Human Molecular Genetics, 2000, Vol. 9, No. 14 2197-2202
© 2000 Oxford University Press
CREB-binding protein sequestration by expanded polyglutamine
Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, 10 Center Drive, Building 10, Room 3B11, Bethesda, MD 20892-1250, USA, 1Department of Neurology, Nagoya University School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi, Japan, 2208 Blumle Life Science Building, Thomas Jefferson University, 233 South 10th Street, Philadelphia, PA 19107, USA and 3Department of Neurology, University of Iowa College of Medicine, 2007 RCP, Iowa City, IA 52242, USA
Received 2 June 2000; Revised and Accepted 10 July 2000.
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ABSTRACT |
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Spinal and bulbar muscular atrophy (SBMA) is one of eight inherited neurodegenerative diseases known to be caused by CAG repeat expansion. The expansion results in an expanded polyglutamine tract, which likely confers a novel, toxic function to the affected protein. Cell culture and transgenic mouse studies have implicated the nucleus as a site for pathogenesis, suggesting that a critical nuclear factor or process is disrupted by the polyglutamine expansion. In this report we present evidence that CREB-binding protein (CBP), a transcriptional co-activator that orchestrates nuclear response to a variety of cell signaling cascades, is incorporated into nuclear inclusions formed by polyglutamine-containing proteins in cultured cells, transgenic mice and tissue from patients with SBMA. We also show CBP incorporation into nuclear inclusions formed in a cell culture model of another polyglutamine disease, spinocerebellar ataxia type 3. We present evidence that soluble levels of CBP are reduced in cells expressing expanded polyglutamine despite increased levels of CBP mRNA. Finally, we demonstrate that over-expression of CBP rescues cells from polyglutamine-mediated toxicity in neuronal cell culture. These data support a CBP-sequestration model of polyglutamine expansion disease.
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONRESULTSDISCUSSIONMATERIALS AND METHODSREFERENCES |
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The polyglutamine diseases are progressive neurodegenerative disorders caused by expansion of trinucleotide (CAG) repeats, encoding polyglutamine tracts, which confer a novel toxic function to the mutant protein. There are at least eight polyglutamine diseases, including spinal and bulbar muscular atrophy (SBMA), which is caused by a CAG expansion in exon 1 of the androgen receptor (AR) gene (1). Expression of truncated AR constructs coding for the expanded polyglutamine tract recapitulates the toxicity in transgenic mice and in cultured cells (2–4). Nuclear inclusions, a pathologic feature of the polyglutamine diseases, can be detected in these models. The role of the nuclear inclusions in the mechanism of the polyglutamine diseases is controversial, but evidence from cellular and transgenic animal models indicates that nuclear localization of the mutant protein is important in toxicity (5,6).
A possible consequence of nuclear accumulation of mutant protein is the sequestration of an important low-abundance nuclear factor such as CREB-binding protein (CBP). CBP and the related protein, p300, are transcriptional co-activators that interact with multiple cell signaling factors, including AP-1 and the nuclear hormone receptors as well as CREB (7, reviewed in ref. 8). These pathways compete for functionally limiting quantities of CBP and, whereas p300 and CBP have many overlapping functions, heterozygous loss of either gene is sufficient to cause severe developmental deficits (9,10).
Biochemical and functional tests show that CBP interacts with the normal AR (11,12). Glutathione-S-transferase pull-down experiments mapped the interaction to both the N- and C-terminal regions of AR (11). Immunoprecipitation of CBP also precipitates AR, and expression of CBP enhances AR-mediated transcription (12). Furthermore, CBP itself contains a polyglutamine tract, which may enhance its interaction with AR and other expanded polyglutamine-containing proteins (13,14). Given the critical role of CBP in cell function, its relatively low abundance, and interaction with the polyglutamine-containing region of AR, we hypothesized that CBP is sequestered to AR-positive nuclear inclusions, and that this sequestration is toxic to the cells. We present evidence that CBP is recruited to polyglutamine inclusions, resulting in a decrease of soluble CBP and CBP-dependent transcription. Furthermore, polyglutamine-induced toxicity is blocked by over-expression of CBP.
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RESULTS |
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TOPABSTRACTINTRODUCTIONRESULTSDISCUSSIONMATERIALS AND METHODSREFERENCES |
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CBP co-localization with polyglutamine inclusions
To examine the effect of polyglutamine on endogenous CBP distribution, we transfected truncated forms of AR with normal and expanded polyglutamine tracts into motor neuron–neuroblastoma hybrid (MN-1) cells. These cells have been found to form nuclear inclusions when expressing mutant AR, and they exhibit repeat length-dependent cell death (3). In this study, AR and CBP distribution was examined by co-immunofluorescence. Transfection with a truncated normal repeat length construct (AR16
) yielded diffuse cytoplasmic AR expression, leaving endogenous CBP evenly distributed in the nucleus, as in non-transfected cells (Fig. 1a–c). In contrast, the product of a truncated expanded repeat construct (AR112) was found both diffusely in the cytoplasm and as inclusion bodies in the nucleus (Fig. 1d). In cells with AR-positive nuclear inclusions, CBP was redistributed to the intranuclear inclusions. The stains completely overlapped when the cells were viewed by traditional fluorescent light microscopy (data not shown). When observed by confocal microscopy, the CBP appeared as a rim around the inclusion bodies (Fig. 1f), suggesting either that CBP was coating the surface of the inclusion or that the antibody could not penetrate the interior of the inclusion. Furthermore, it appeared that much of the CBP was recruited to the inclusions, as the remaining CBP stain in the nucleus was reduced to background levels. Nearly all the AR-positive nuclear inclusions were CBP positive, although no CBP staining was observed in the cytoplasm, confirming that the stain was specific to CBP and not caused by an interaction between the CBP and AR antibodies.
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CBP sequestration was not limited to inclusions formed by mutant AR. In a similar experiment, HeLa cells were transfected with either normal or mutant full-length ataxin-3, the disease gene product in spinocerebellar ataxia 3. Normal ataxin-3 was found diffusely in the cytoplasm and nucleus, whereas mutant ataxin-3 formed nuclear inclusions (Fig. 1g). In cells with nuclear inclusions, CBP was again redistributed from a pan-nuclear pattern to concentration within the ataxin-3 inclusions (Fig. 1g–i). Similar results were obtained in PC12 cells transfected with full-length ataxin-3 (data not shown).
We extended these results by looking at CBP distribution in transgenic mice expressing AR112 driven by the prion protein promoter (4). Mice expressing AR112 have intranuclear inclusions in neurons throughout the brain. CBP- and AR-positive inclusions were observed in adjacent sections (data not shown). Co-immunofluorescent staining showed that about half (120/223) of the AR-positive inclusions were also CBP positive.
CBP distribution was also examined in SBMA patient tissue. Scrotal skin samples were used because of the abundance of nuclear aggregates found in this tissue (15). CBP and AR staining in frozen sections showed that CBP co-localizes with AR-positive inclusions in the keratinocytes (Fig. 2). Again, the rate of co-localization was high, with 58 of 120 AR-positive inclusions staining positively for CBP. In addition, there were CBP-positive inclusions that did not stain for AR. This may have been due to the AR epitope being obscured by the inclusion or to low frequency detection of other CBP-containing nuclear bodies.
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Soluble CBP is decreased in AR112 cells
To confirm the observation that much of CBP is redistributed to the inclusions, we assayed soluble CBP protein levels. In order to enhance endogenous CBP signal strength, western blotting was preceded by immunoprecipitation. CBP levels were markedly lower in cells expressing a truncated, expanded repeat length construct tagged with green fluorescent protein (GFP) (AR112–GFP) (Fig. 3a). To determine whether the decrease in protein was caused by decreased production of CBP, the CBP transcript levels were examined. We found that CBP transcription was slightly up-regulated (40%) in the presence of AR112–GFP (Fig. 3b) compared with glyceraldehyde 3-phosphate dehydrogenase (GAPDH) transcript levels (data not shown). This mild increase indicates that the cellular response to CBP depletion was limited, and that most of the soluble CBP was recruited to the inclusions.
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CBP-dependent transcription is decreased
Since CBP is an important co-activator for transcription, CBP function was assayed by measuring the ability of a Gal4–CBP fusion construct to drive transcription from a reporter construct (G5–luc) with Gal4 response elements driving expression of the firefly luciferase gene. Transfection of these constructs resulted in high levels of luciferase activity. In the presence of vector alone [cytomegalovirus (CMV)–GFP] or a truncated normal repeat length construct (AR19–GFP), luciferase was reduced to 30% of the activity found in cells with Gal4–CBP and G5–luc alone (8- to 10-fold over background). We attribute this decrease to elements in the CMV promoter. AR112–GFP further reduced luciferase activity to near background levels (Fig. 4a), indicating that the Gal4–CBP was sequestered and thus not available to drive transcription.
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CBP blocks polyglutamine induced toxicity
Lastly, to determine whether the sequestration of CBP was responsible for cellular toxicity, we measured the effect of CBP over-expression in cells transfected with polyglutamine-containing AR constructs. As reported previously (3), cells expressing expanded polyglutamine died over 48–72 h (Fig. 4b). Cells over-expressing exogenous CBP showed enhanced viability, and the toxic effect of the expanded polyglutamine was blocked (Fig. 4c). CBP failed to rescue cells co-transfected with constructs for the pro-apoptotic factor bax (data not shown), indicating that the CBP was not simply having a non-specific effect on cellular toxicity.
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DISCUSSION |
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We have found that CBP, normally present in a diffuse nuclear pattern, is sequestered in nuclear inclusions formed in cells expressing expanded polyglutamine proteins. This sequestration is found not only in cultured cells, but also in transgenic mice and patient tissue, and is common to at least two of the polyglutamine disorders. The ability of over-expressed CBP to block polyglutamine-induced toxicity in cell culture suggests that this sequestration may be an important step in the disease pathogenesis.
CBP as a general target in polyglutamine disease
CBP is a particularly good candidate gene for disruption, as it is present at functionally limiting levels in the cell. Mice lacking one allele of the CBP gene have pronounced developmental defects, despite the presence of the second allele and two copies of the gene for p300, a protein thought to be largely redundant with CBP. Furthermore, ample evidence indicates that different cell signaling pathways compete for use of CBP in driving different transcriptional programs that influence cell proliferation and survival. Our finding that over-expression of CBP blocks polyglutamine-induced toxicity in these cells suggests that the toxicity is due to CBP depletion.
Recently, CBP was shown to co-localize with mutant huntingtin in cells co-transfected with plasmids for both genes (14). The recruitment of CBP to the inclusions in this study was dependent on the polyglutamine domain of CBP. This domain is in the C-terminal region of the protein and consists of 18 glutamines in humans and 15 in mice. Furthermore, CBP has been found in nuclear inclusions formed in mice transgenic for exon 1 of huntingtin (16). Importantly, the CBP antibodies used in both studies were raised against an epitope that does not include the polyglutamine repeat. Finding that CBP binds to huntingtin-positive inclusions, together with our evidence that it binds to AR- and ataxin-3-positive inclusions, indicates that CBP sequestration may be a general phenomenon of polyglutamine expansion diseases.
CBP and nuclear inclusions
We have used nuclear inclusions as a marker for pathological changes in the interactions of CBP; however, it is not necessary that nuclear inclusions directly cause toxicity for the CBP sequestration or any other sequestration model to be valid. Instead, redistribution of CBP to inclusions, and the concomitant decrease in CBP-dependent transcription, only show that polyglutamine-containing proteins bind CBP sufficiently to suppress CBP-dependent processes. The sequestration model is dependent only on decreased turnover of polyglutamine-containing proteins in the nucleus, as could result from the formation of nuclear inclusions or from impaired proteasome-mediated degradation. In this regard, our data are supported by recent evidence showing that disruption of ataxin-1 ubiquitination, a necessary step in targeting proteins for degradation, enhances toxicity in mice transgenic for mutant ataxin-1 (17).
CBP and transcription
Whereas CBP co-localizes with AR-positive inclusions in nearly 100% of the nuclear inclusions formed in cell culture, it is only found in 
50% of the nuclear inclusions in the mouse and patient tissue. The percent overlap is probably an underestimate, in particular in the patient tissue, as CBP-positive, AR-negative inclusions were also observed.
There are several possible explanations for the CBP-positive, AR-negative inclusions. The AR epitope may be masked, or sequestered in the interior of the inclusion. This is supported by our observation that the inclusions stain as ring-like structures in tissue culture. Another possibility is that the CBP-positive inclusions are altered promyelocytic (PML) oncogenic domains.
In addition to CBP, other components of the transcription apparatus interact specifically with polyglutamine-containing proteins. PML, nuclear co-repressor (NCoR), steroid receptor co-activator and glucocorticoid receptor interacting protein 1 have all been shown to differentially interact with expanded polyglutamine-containing proteins (18–20). Each of these proteins (including CBP) influences chromatin condensation by altering histone acetylation (21). Decreases in histone acetylation might result in toxicity by broadly disrupting transcriptional regulation.
In contrast to the other interacting factors, CBP has been implicated in mediating signals critical for neuronal survival. CREB, whose transcriptional activity is mediated by CBP, has been identified as a critical component of neuronal responses to neurotrophins (22,23). CBP has been directly linked to neuronal responses to nerve growth factor (NGF) in studies showing up-regulation in CBP-dependent transcriptional activity in the presence of NGF (24). One possible mechanism for polyglutamine disease is that as CBP is sequestered, neuronal response to trophic factors essential for survival is diminished. Our data showing a decrease in soluble CBP in the presence of expanded polyglutamine and the ability of exogenous CBP to rescue cells from polyglutamine-induced toxicity indicate a central role for CBP in the pathogenesis of polyglutamine-expansion diseases.
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MATERIALS AND METHODS |
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Co-localization of CBP with AR
MN-1 cells were grown as described (25) and transfected with previously reported AR constructs (3), using the GenePorter reagent (Gene Therapy Systems, San Diego, CA). AR was visualized by immunofluorescence, using N-20 (Santa Cruz Biotechnology, Santa Cruz, CA), a rabbit polyclonal antibody directed against the first 20 amino acids, and fluorescein isothiocyanate (FITC)-conjugated donkey anti-rabbit secondary antibody (Jackson ImmunoResearch, West Grove, PA). Endogenous CBP was visualized with C-1 (Santa Cruz), a mouse monoclonal antibody directed against the last 12 amino acids, and Cy5-conjugated donkey anti-mouse secondary antibody (Jackson ImmunoResearch). Images were taken at the Confocal Imaging Facility of the National Institute of Neurological Disorders and Stroke.
Full-length ataxin-3, expressed in transiently transfected HeLa cells, was stained with an anti-ataxin-3 rabbit polyclonal antibody (26) and visualized with FITC-conjugated donkey anti-rabbit secondary antibody (Jackson ImmunoResearch). In these experiments, the secondary antibody for C-1 was tetramethyl rhodamine isothiocyanate conjugated. Images were taken with traditional fluorescent microscopy at the University of Iowa.
The transgenic mice were generated with the prion promoter driving expression of the same AR constructs as used in the cell culture experiments (4). AR was stained with the N-20 antibody and horseradish peroxidase-conjugated secondary antibody. Adjacent sections were stained for CBP with C-1. Samples were viewed under Nomarski optics.
Immunohistochemistry of AR and CBP in human tissue followed standard procedures. C-1 antibody was applied to a 4 µm thick frozen section of the scrotal skin of an SBMA patient, incubated overnight and visualized with fast red. After photography, the slide was stripped with 0.3% H2O2 in methanol, then incubated overnight with the N-20 antibody and visualized with diaminobenzidene.
Gal4–CBP-mediated transcription
CBP depletion was measured in HEK-293 cells by assaying the Gal4-mediated transcriptional activity of a Gal4–CBP fusion protein. The cells were co-transfected with Gal4–CBP (a gift from Azad Bonni, Harvard University), G5-firefly luciferase reporter plasmid (Stratagene, La Jolla, CA) and a plasmid encoding sea pansy luciferase (Promega, Madison, WI). The sea pansy luciferase was used as a control for transfection efficiency and cell viability. In addition, the cells were transfected with constructs for vector alone (CMV–GFP), normal polyglutamine (AR19–GFP) or expanded polyglutamine (AR112–GFP). These constructs were derived from previously described AR cDNA clones (3), by subcloning an XbaI–EcoRI fragment into the N1–GFP vector (Clontech, Palo Alto, CA). After 48 h, cells were harvested and lysed. Addition of substrate permitted both firefly and sea pansy luciferase activity to be measured as relative light units, and the firefly luciferase activity was normalized to sea pansy activity.
CBP transcript and protein levels
CBP transcript levels were determined by northern blot. RNA was harvested from HEK-293 cells transfected with AR19–GFP or AR112–GFP using the RNeasy kit (Qiagen, Valencia, CA). The samples were run on a denaturing gel, then transferred overnight to a ZetaProbe GT blotting membrane (Bio-Rad, Hercules, CA). The probe for CBP was generated by cutting pcDNA3.1-CBP (27) with EcoRI–BamHI and labeling with the RediPrime kit (Amersham Pharmacia, Indianapolis, IN). After washing, the membrane was exposed to a phosphoimaging plate for 12 h. The plate was scanned with a Molecular Dynamics Storm 860 imaging system, and the bands were quantified using the ImageQuant v1.2 software package (Molecular Dynamics, Sunnyvale, CA). The membrane was stripped and probed for the GAPDH transcript to confirm equal loading and transfer.
CBP protein levels were measured by immunoprecipitating CBP from MN-1 cell lysates using the anti-CBP-CT antibody from Upstate Biotechnology (Lake Placid, NY). The immunoprecipitation was performed by the manufacturer’s protocol. Following immunoprecipitation, samples were run on 7.5% SDS–polyacrylamide gel. CBP was detected using anti-mouse CBP-CT, with horseradish peroxidase-conjugated donkey anti-mouse secondary. Bands were visualized by enhanced chemiluminescence (NEN Life Science Products, Boston, MA). Protein levels were normalized before immunoprecipitation by DC assay (Bio-Rad), and prominent background bands were compared after development to insure comparable loading levels.
Cell viability assay
Cell viability was measured by reduction of the tetrazolium salt [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) (Sigma, St Louis, MO)]. Briefly, HEK-293 cells were transfected with truncated AR constructs, including the polyglutamine repeat, with and without full-length CBP (27), and plated in 96-well plates. MTT (5 mg/ml) was added at 24, 48 and 72 h, and the cells were incubated for 2 h. The resultant crystals were dissolved in a solution of 20% SDS in 50% dimethyl formamide. The optical density was measured at 570 nm and normalized to controls transfected with vector alone.
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ACKNOWLEDGEMENTS |
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We thank Drs Richard Goodman, Azad Bonni and Richard Youle for constructs, and Carol Smith for assistance with confocal microscopy. J.R. was supported by the Howard Hughes Medical Institute through the NIH Research Scholars program. This work was supported by intramural funds of the National Institute for Neurological Disorders and Stroke.
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FOOTNOTES |
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+ To whom correspondence should be addressed. Tel: +1 301 435 9288; Fax: +1 301 480 3365; Email: mccampba@ninds.nih.gov
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REFERENCES |
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1 La Spada, A.R., Wilson, E.M., Lubahn, D.B., Harding, A.E. and Fischbeck, K.H. (1991) Androgen receptor gene mutations in X-linked spinal and bulbar muscular atrophy. Nature, 352, 77–79.[Medline]
2 Brooks, B.P., Paulson, H.L., Merry, D.E., Salazar-Grueso, E.F., Brinkmann, A.O., Wilson, E.M. and Fischbeck, K.H. (1997) Characterization of an expanded glutamine repeat androgen receptor in a neuronal cell culture system. Neurobiol. Dis., 3, 313–323.[Web of Science][Medline]
3 Merry, D.E., Kobayashi, Y., Bailey, C.K., Taye, A.A. and Fischbeck, K.H. (1998) Cleavage, aggregation and toxicity of the expanded androgen receptor in spinal and bulbar muscular atrophy. Hum. Mol. Genet., 7, 693–701.
4 Merry, D.E., Woods, J., Walcott, J., Bish, L., Fischbeck, K.H. and Abel, A. (1999) Characterization of a transgenic model for SBMA. Am. J. Hum. Genet., 65, 153S.
5 Klement, I.A., Skinner, P.J., Kaytor, M.D., Yi, H., Hersch, S.M., Clark, H.B., Zoghbi, H.Y. and Orr, H.T. (1998) Ataxin-1 nuclear localization and aggregation: role in polyglutamine-induced disease in SCA1 transgenic mice. Cell, 95, 41–53.[Web of Science][Medline]
6 Saudou, F., Finkbeiner, S., Devys, D. and Greenberg, M.E. (1998) Huntingtin acts in the nucleus to induce apoptosis but death does not correlate with the formation of intranuclear inclusions. Cell, 95, 55–66.[Web of Science][Medline]
7 Kamei, Y., Xu, L., Heinzel, T., Torchia, J., Kurokawa, R., Gloss, B., Lin, S.C., Heyman, R.A., Rose, D.W., Glass, C.K. and Rosenfeld, M.G. (1996) A CBP integrator complex mediates transcriptional activation and AP-1 inhibition by nuclear receptors. Cell, 85, 403–414.[Web of Science][Medline]
8 Shikama, N., Lyon, J. and LaThangue, N. (1997) The p300/CBP family: integrating signals with transcription factors and chromatin. Trends Cell Biol., 7, 230–236.
9 Yao, T.P., Oh, S.P., Fuchs, M., Zhou, N.D., Ch’ng, L.E., Newsome, D., Bronson, R.T., Li, E., Livingston, D.M. and Eckner, R. (1998) Gene dosage-dependent embryonic development and proliferation defects in mice lacking the transcriptional integrator p300. Cell, 93, 361–372.[Web of Science][Medline]
10 Tanaka, Y., Naruse, I., Maekawa, T., Masuya, H., Shiroishi, T. and Ishii, S. (1997) Abnormal skeletal patterning in embryos lacking a single CBP allele: a partial similarity with Rubinstein-Taybi syndrome. Proc. Natl Acad. Sci. USA, 94, 10215–10220.
11 Fronsdal, K., Engedal, N., Slagsvold, T. and Saatcioglu, F. (1998) CREB binding protein is a coactivator for the androgen receptor and mediates cross-talk with AP-1. J. Biol. Chem., 273, 31853–31859.
12 Aarnisalo, P., Palvimo, J.J. and Janne, O.A. (1998) CREB-binding protein in androgen receptor-mediated signaling. Proc. Natl Acad. Sci. USA, 95, 2122–2127.
13 Perez, M.K., Paulson, H.L., Pendse, S.J., Saionz, S.J., Bonini, N.M. and Pittman, R.N. (1998) Recruitment and the role of nuclear localization in polyglutamine-mediated aggregation. J. Cell Biol., 143, 1457–1470.
14 Kazantsev, A., Preisinger, E., Dranovsky, A., Goldgaber, D. and Housman, D. (1999) Insoluble detergent-resistant aggregates form between pathological and nonpathological lengths of polyglutamine in mammalian cells. Proc. Natl Acad. Sci. USA, 96, 11404–11409.
15 Li, M., Nakagomi, Y., Kobayashi, Y., Merry, D.E., Tanaka, F., Doyu, M., Mitsuma, T., Hashizume, Y., Fischbeck, K.H. and Sobue G. (1998) Nonneural nuclear inclusions of androgen receptor protein in spinal and bulbar muscular atrophy. Am. J. Pathol., 153, 695–701.
16 Steffan, J.S., Kazantsev, A., Spasic-boskovic, O., Greenwald, M., Zhu, Y.-Z., Gohler, H., Wanker, E.E., Bates, G.P., Housman, D.E. and Thompson, L.M. (2000) The Huntington’s disease protein interacts with p53 and CREB-binding protein and represses transcription. Proc. Natl Acad. Sci. USA, 97, 6763–6768.
17 Cummings, C.J., Reinstein, E., Sun, Y., Antalffy, B., Jiang, Y., Ciechanover, A., Orr, H.T., Beaudet, A.L. and Zoghbi, H.Y. (1999) Mutation of the E6-AP ubiquitin ligase reduces nuclear inclusion frequency while accelerating polyglutamine-induced pathology in SCA1 mice. Neuron, 24, 879–892.[Web of Science][Medline]
18 Boutell, J.M., Thomas, P., Neal, J.W., Weston, V.J., Duce, J., Harper, P.S. and Jones, A.L. (1999) Aberrant interactions of transcriptional repressor proteins with the Huntington’s disease gene product, huntingtin. Hum. Mol. Genet., 8, 1647–1655.
19 Stenoien, D.L., Cummings, C.J., Adams, H.P., Mancini, M.G., Patel, K., DeMartino, G.N., Marcelli, M., Weigel, N.L. and Mancini, M.A. (1999) Polyglutamine-expanded androgen receptors form aggregates that sequester heat shock proteins, proteasome components and SRC-1, and are suppressed by the HDJ-2 chaperone. Hum. Mol. Genet., 8, 731–741.
20 Irvine, R.A., Ma, H., Yu, M.C., Ross, R.K., Stallcup, M.R. and Coetzee, G.A. (2000) Inhibition of p160-mediated coactivation with increasing androgen receptor polyglutamine length. Hum. Mol. Genet., 9, 267–274.
21 Collingwood, T.N., Urnov, F.D. and Wolffe, A.P. (1999) Nuclear receptors: coactivators, corepressors and chromatin remodeling in the control of transcription. J. Mol. Endocrinol., 23, 255–275.[Abstract]
22 Bonni, A., Brunet, A., West, A.E., Datta, S.R., Takasu, M.A. and Greenberg, M.E. (1999) Cell survival promoted by the Ras-MAPK signaling pathway by transcription-dependent and -independent mechanisms. Science, 286, 1358–1362.
23 Riccio, A., Ahn, S., Davenport, C.M., Blendy, J.A. and Ginty, D.D. (1999) Mediation by a CREB family transcription factor of NGF-dependent survival of sympathetic neurons. Science, 286, 2358–2361.
24 Liu, Y.Z., Chrivia, J.C. and Latchman, D.S. (1998) Nerve growth factor up-regulates the transcriptional activity of CBP through activation of the p42/p44(MAPK) cascade. J. Biol. Chem., 273, 32400–32407.
25 Salazar-Grueso, E.F., Kim, S. and Kim, H. (1991) Embryonic mouse spinal cord motor neuron hybrid cells. Neuroreport, 2, 505–508.[Web of Science][Medline]
26 Chai, Y., Koppenhafer, S.L., Shoesmith, S.J., Perez, M.K. and Paulson, H.L. (1998) Evidence for proteasome involvement in polyglutamine disease: localization to nuclear inclusions in SCA3/MJD and suppression of polyglutamine aggregation in vitro. Hum. Mol. Genet., 8, 673–682.
27 Kwok, R.P., Lundblad, J.R., Chrivia, J.C., Richards, J.P., Bachinger, H.P., Brennan, R.G., Roberts, S.G., Green, M.R. and Goodman, R.H. (1994) Nuclear protein CBP is a coactivator for the transcription factor CREB. Nature, 370, 223–226.[Medline]
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 T. Gidalevitz, A. Ben-Zvi, K. H. Ho, H. R. Brignull, and R. I. Morimoto Progressive Disruption of Cellular Protein Folding in Models of Polyglutamine Diseases Science, March 10, 2006; 311(5766): 1471 - 1474. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. A. Bates, M. Victor, A. K. Jones, Y. Shi, and A. C. Hart Differential contributions of Caenorhabditis elegans histone deacetylases to huntingtin polyglutamine toxicity. J. Neurosci., March 8, 2006; 26(10): 2830 - 2838. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Yu, N. Dadgar, M. Albertelli, A. Scheller, R. L. Albin, D. M. Robins, and A. P. Lieberman Abnormalities of Germ Cell Maturation and Sertoli Cell Cytoskeleton in Androgen Receptor 113 CAG Knock-In Mice Reveal Toxic Effects of the Mutant Protein Am. J. Pathol., January 1, 2006; 168(1): 195 - 204. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Iijima-Ando, P. Wu, E. A. Drier, K. Iijima, and J. C. P. Yin cAMP-response element-binding protein and heat-shock protein 70 additively suppress polyglutamine-mediated toxicity in Drosophila PNAS, July 19, 2005; 102(29): 10261 - 10266. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Thomas, Z. Yu, N. Dadgar, S. Varambally, J. Yu, A. M. Chinnaiyan, and A. P. Lieberman The Unfolded Protein Response Modulates Toxicity of the Expanded Glutamine Androgen Receptor J. Biol. Chem., June 3, 2005; 280(22): 21264 - 21271. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Adachi, M. Katsuno, M. Minamiyama, M. Waza, C. Sang, Y. Nakagomi, Y. Kobayashi, F. Tanaka, M. Doyu, A. Inukai, et al. Widespread nuclear and cytoplasmic accumulation of mutant androgen receptor in SBMA patients Brain, March 1, 2005; 128(3): 659 - 670. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. B. Kindle, P. J. F. Troke, H. M. Collins, S. Matsuda, D. Bossi, C. Bellodi, E. Kalkhoven, P. Salomoni, P. G. Pelicci, S. Minucci, et al. MOZ-TIF2 Inhibits Transcription by Nuclear Receptors and p53 by Impairment of CBP Function Mol. Cell. Biol., February 1, 2005; 25(3): 988 - 1002. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. M. Everett and N. W. Wood Trinucleotide repeats and neurodegenerative disease Brain, November 1, 2004; 127(11): 2385 - 2405. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S.-H. Li and X.-J. Li Huntington and its Role in Neuronal Degeneration Neuroscientist, October 1, 2004; 10(5): 467 - 475. [Abstract] [PDF]
|
|
|
|
 |
|
 X.-C. Zeng, S. Bhasin, X. Wu, J.-G. Lee, S. Maffi, C. J. Nichols, K. J. Lee, J. P. Taylor, L. E. Greene, and E. Eisenberg Hsp70 dynamics in vivo: effect of heat shock and protein aggregation J. Cell Sci., October 1, 2004; 117(21): 4991 - 5000. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Buchanan, M. Yang, A. Cheong, J. M. Harris, R. A. Irvine, P. F. Lambert, N. L. Moore, M. Raynor, P. J. Neufing, G. A. Coetzee, et al. Structural and functional consequences of glutamine tract variation in the androgen receptor Hum. Mol. Genet., August 15, 2004; 13(16): 1677 - 1692. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Minamiyama, M. Katsuno, H. Adachi, M. Waza, C. Sang, Y. Kobayashi, F. Tanaka, M. Doyu, A. Inukai, and G. Sobue Sodium butyrate ameliorates phenotypic expression in a transgenic mouse model of spinal and bulbar muscular atrophy Hum. Mol. Genet., June 1, 2004; 13(11): 1183 - 1192. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C.-C. Tsai, H.-Y. Kao, A. Mitzutani, E. Banayo, H. Rajan, M. McKeown, and R. M. Evans Ataxin 1, a SCA1 neurodegenerative disorder protein, is functionally linked to the silencing mediator of retinoid and thyroid hormone receptors PNAS, March 23, 2004; 101(12): 4047 - 4052. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Thomas, N. Dadgar, A. Aphale, J. M. Harrell, R. Kunkel, W. B. Pratt, and A. P. Lieberman Androgen Receptor Acetylation Site Mutations Cause Trafficking Defects, Misfolding, and Aggregation Similar to Expanded Glutamine Tracts J. Biol. Chem., February 27, 2004; 279(9): 8389 - 8395. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. L. Sugars, R. Brown, L. J. Cook, J. Swartz, and D. C. Rubinsztein Decreased cAMP Response Element-mediated Transcription: AN EARLY EVENT IN EXON 1 AND FULL-LENGTH CELL MODELS OF HUNTINGTON'S DISEASE THAT CONTRIBUTES TO POLYGLUTAMINE PATHOGENESIS J. Biol. Chem., February 6, 2004; 279(6): 4988 - 4999. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Chai, S. S. Berke, R. E. Cohen, and H. L. Paulson Poly-ubiquitin Binding by the Polyglutamine Disease Protein Ataxin-3 Links Its Normal Function to Protein Surveillance Pathways J. Biol. Chem., January 30, 2004; 279(5): 3605 - 3611. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Obrietan and K. R. Hoyt CRE-Mediated Transcription Is Increased in Huntington's Disease Transgenic Mice J. Neurosci., January 28, 2004; 24(4): 791 - 796. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Chen, G.-H. Peng, X. Wang, A. C. Smith, S. K. Grote, B. L. Sopher, and A. R. La Spada Interference of Crx-dependent transcription by ataxin-7 involves interaction between the glutamine regions and requires the ataxin-7 carboxy-terminal region for nuclear localization Hum. Mol. Genet., January 1, 2004; 13(1): 53 - 67. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. J. Ferrante, J. K. Kubilus, J. Lee, H. Ryu, A. Beesen, B. Zucker, K. Smith, N. W. Kowall, R. R. Ratan, R. Luthi-Carter, et al. Histone Deacetylase Inhibition by Sodium Butyrate Chemotherapy Ameliorates the Neurodegenerative Phenotype in Huntington's Disease Mice J. Neurosci., October 15, 2003; 23(28): 9418 - 9427. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Michalik and C. Van Broeckhoven Pathogenesis of polyglutamine disorders: aggregation revisited Hum. Mol. Genet., October 15, 2003; 12(90002): R173 - 186. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Okamura-Oho, T. Miyashita, K. Nagao, S. Shima, Y. Ogata, T. Katada, H. Nishina, and M. Yamada Dentatorubral-pallidoluysian atrophy protein is phosphorylated by c-Jun NH2-terminal kinase Hum. Mol. Genet., July 1, 2003; 12(13): 1535 - 1542. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Ishihara, N. Yamagishi, Y. Saito, H. Adachi, Y. Kobayashi, G. Sobue, K. Ohtsuka, and T. Hatayama Hsp105{alpha} Suppresses the Aggregation of Truncated Androgen Receptor with Expanded CAG Repeats and Cell Toxicity J. Biol. Chem., June 27, 2003; 278(27): 25143 - 25150. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. P. Taylor, A. A. Taye, C. Campbell, P. Kazemi-Esfarjani, K. H. Fischbeck, and K.-T. Min Aberrant histone acetylation, altered transcription, and retinal degeneration in a Drosophila model of polyglutamine disease are rescued by CREB-binding protein Genes & Dev., June 15, 2003; 17(12): 1463 - 1468. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. C. Tsai, P. S. Fishman, N. V. Thakor, and G. A. Oyler Parkin Facilitates the Elimination of Expanded Polyglutamine Proteins and Leads to Preservation of Proteasome Function J. Biol. Chem., June 6, 2003; 278(24): 22044 - 22055. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Nagai, N. Fujikake, K. Ohno, H. Higashiyama, H. A. Popiel, J. Rahadian, M. Yamaguchi, W. J. Strittmatter, J. R. Burke, and T. Toda Prevention of polyglutamine oligomerization and neurodegeneration by the peptide inhibitor QBP1 in Drosophila Hum. Mol. Genet., June 1, 2003; 12(11): 1253 - 1259. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Okuda, H. Hattori, S. Takeuchi, J. Shimizu, H. Ueda, J. J. Palvimo, I. Kanazawa, H. Kawano, M. Nakagawa, and H. Okazawa PQBP-1 transgenic mice show a late-onset motor neuron disease-like phenotype Hum. Mol. Genet., April 1, 2003; 12(7): 711 - 725. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. P. Taylor, F. Tanaka, J. Robitschek, C. M. Sandoval, A. Taye, S. Markovic-Plese, and K. H. Fischbeck Aggresomes protect cells by enhancing the degradation of toxic polyglutamine-containing protein Hum. Mol. Genet., April 1, 2003; 12(7): 749 - 757. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Adachi, M. Katsuno, M. Minamiyama, C. Sang, G. Pagoulatos, C. Angelidis, M. Kusakabe, A. Yoshiki, Y. Kobayashi, M. Doyu, et al. Heat Shock Protein 70 Chaperone Overexpression Ameliorates Phenotypes of the Spinal and Bulbar Muscular Atrophy Transgenic Mouse Model by Reducing Nuclear-Localized Mutant Androgen Receptor Protein J. Neurosci., March 15, 2003; 23(6): 2203 - 2211. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Gines, I. S. Seong, E. Fossale, E. Ivanova, F. Trettel, J. F. Gusella, V. C. Wheeler, F. Persichetti, and M. E. MacDonald Specific progressive cAMP reduction implicates energy deficit in presymptomatic Huntington's disease knock-in mice Hum. Mol. Genet., March 1, 2003; 12(5): 497 - 508. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. A. Ross, M. A. Poirier, E. E. Wanker, and M. Amzel Polyglutamine fibrillogenesis: The pathway unfolds PNAS, January 7, 2003; 100(1): 1 - 3. [Full Text] [PDF]
|
|
|
|
|
|
H. Jiang, F. C. Nucifora Jr, C. A. Ross, and D. B. DeFranco Cell death triggered by polyglutamine-expanded huntingtin in a neuronal cell line is associated with degradation of CREB-binding protein Hum. Mol. Genet., January 1, 2003; 12(1): 1 - 12. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. W. Faber, C. Voisine, D. C. King, E. A. Bates, and A. C. Hart Glutamine/proline-rich PQE-1 proteins protect Caenorhabditis elegans neurons from huntingtin polyglutamine neurotoxicity PNAS, December 24, 2002; 99(26): 17131 - 17136. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Li, T. Macfarlan, R. N. Pittman, and D. Chakravarti Ataxin-3 Is a Histone-binding Protein with Two Independent Transcriptional Corepressor Activities J. Biol. Chem., November 15, 2002; 277(47): 45004 - 45012. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Kazemi-Esfarjani and S. Benzer Suppression of polyglutamine toxicity by a Drosophila homolog of myeloid leukemia factor 1 Hum. Mol. Genet., October 2, 2002; 11(21): 2657 - 2672. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Kimura, S. Koitabashi, A. Kakizuka, and T. Fujita Circumvention of Chaperone Requirement for Aggregate Formation of a Short Polyglutamine Tract by the Co-expression of a Long Polyglutamine Tract J. Biol. Chem., September 27, 2002; 277(40): 37536 - 37541. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Fossale, V. C. Wheeler, V. Vrbanac, L.-A. Lebel, A. Teed, J. S. Mysore, J. F. Gusella, M. E. MacDonald, and F. Persichetti Identification of a presymptomatic molecular phenotype in Hdh CAG knock-in mice Hum. Mol. Genet., September 15, 2002; 11(19): 2233 - 2241. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Kita, J. Carmichael, J. Swartz, S. Muro, A. Wyttenbach, K. Matsubara, D. C. Rubinsztein, and K. Kato Modulation of polyglutamine-induced cell death by genes identified by expression profiling Hum. Mol. Genet., September 15, 2002; 11(19): 2279 - 2287. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Luthi-Carter, S. A. Hanson, A. D. Strand, D. A. Bergstrom, W. Chun, N. L. Peters, A. M. Woods, E. Y. Chan, C. Kooperberg, D. Krainc, et al. Dysregulation of gene expression in the R6/2 model of polyglutamine disease: parallel changes in muscle and brain Hum. Mol. Genet., August 15, 2002; 11(17): 1911 - 1926. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Luthi-Carter, A. D. Strand, S. A. Hanson, C. Kooperberg, G. Schilling, A. R. La Spada, D. E. Merry, A. B. Young, C. A. Ross, D. R. Borchelt, et al. Polyglutamine and transcription: gene expression changes shared by DRPLA and Huntington's disease mouse models reveal context-independent effects Hum. Mol. Genet., August 15, 2002; 11(17): 1927 - 1937. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. P. Lieberman, G. Harmison, A. D. Strand, J. M. Olson, and K. H. Fischbeck Altered transcriptional regulation in cells expressing the expanded polyglutamine androgen receptor Hum. Mol. Genet., August 15, 2002; 11(17): 1967 - 1976. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Chai, J. Shao, V. M. Miller, A. Williams, and H. L. Paulson Live-cell imaging reveals divergent intracellular dynamics of polyglutamine disease proteins and supports a sequestration model of pathogenesis PNAS, July 9, 2002; 99(14): 9310 - 9315. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Takahashi, H. Fujigasaki, C. Zander, K. H. El Hachimi, G. Stevanin, A. Durr, A.-S. Lebre, G. Yvert, Y. Trottier, H. d. The, et al. Two populations of neuronal intranuclear inclusions in SCA7 differ in size and promyelocytic leukaemia protein content Brain, July 1, 2002; 125(7): 1534 - 1543. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. A. Garden, R. T. Libby, Y.-H. Fu, Y. Kinoshita, J. Huang, D. E. Possin, A. C. Smith, R. A. Martinez, G. C. Fine, S. K. Grote, et al. Polyglutamine-Expanded Ataxin-7 Promotes Non-Cell-Autonomous Purkinje Cell Degeneration and Displays Proteolytic Cleavage in Ataxic Transgenic Mice J. Neurosci., June 15, 2002; 22(12): 4897 - 4905. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z.-X. Yu, S.-H. Li, H.-P. Nguyen, and X.-J. Li Huntingtin inclusions do not deplete polyglutamine-containing transcription factors in HD mice Hum. Mol. Genet., April 15, 2002; 11(8): 905 - 914. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. K. Bailey, I. F. M. Andriola, H. H. Kampinga, and D. E. Merry Molecular chaperones enhance the degradation of expanded polyglutamine repeat androgen receptor in a cellular model of spinal and bulbar muscular atrophy Hum. Mol. Genet., March 1, 2002; 11(5): 515 - 523. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. J. Welch and M. I. Diamond Glucocorticoid modulation of androgen receptor nuclear aggregation and cellular toxicity is associated with distinct forms of soluble expanded polyglutamine protein Hum. Mol. Genet., December 1, 2001; 10(26): 3063 - 3074. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Yamada, T. Sato, T. Shimohata, S. Hayashi, S. Igarashi, S. Tsuji, and H. Takahashi Interaction between Neuronal Intranuclear Inclusions and Promyelocytic Leukemia Protein Nuclear and Coiled Bodies in CAG Repeat Diseases Am. J. Pathol., November 1, 2001; 159(5): 1785 - 1795. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Sathasivam, B. Woodman, A. Mahal, F. Bertaux, E. E. Wanker, D. T. Shima, and G. P. Bates Centrosome disorganization in fibroblast cultures derived from R6/2 Huntington's disease (HD) transgenic mice and HD patients Hum. Mol. Genet., October 1, 2001; 10(21): 2425 - 2435. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Yvert, K. S. Lindenberg, D. Devys, D. Helmlinger, G. B. Landwehrmeyer, and J.-L. Mandel SCA7 mouse models show selective stabilization of mutant ataxin-7 and similar cellular responses in different neuronal cell types Hum. Mol. Genet., August 1, 2001; 10(16): 1679 - 1692. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Wyttenbach, J. Swartz, H. Kita, T. Thykjaer, J. Carmichael, J. Bradley, R. Brown, M. Maxwell, A. Schapira, T. F. Orntoft, et al. Polyglutamine expansions cause decreased CRE-mediated transcription and early gene expression changes prior to cell death in an inducible cell model of Huntington's disease Hum. Mol. Genet., August 1, 2001; 10(17): 1829 - 1845. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. O. Evert, I. R. Vogt, C. Kindermann, L. Ozimek, R. A. I. de Vos, E. R. P. Brunt, I. Schmitt, T. Klockgether, and U. Wullner Inflammatory Genes Are Upregulated in Expanded Ataxin-3-Expressing Cell Lines and Spinocerebellar Ataxia Type 3 Brains J. Neurosci., August 1, 2001; 21(15): 5389 - 5396. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Adachi, A. Kume, M. Li, Y. Nakagomi, H. Niwa, J. Do, C. Sang, Y. Kobayashi, M. Doyu, and G. Sobue Transgenic mice with an expanded CAG repeat controlled by the human AR promoter show polyglutamine nuclear inclusions and neuronal dysfunction without neuronal cell death Hum. Mol. Genet., May 1, 2001; 10(10): 1039 - 1048. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. C. Nucifora Jr., M. Sasaki, M. F. Peters, H. Huang, J. K. Cooper, M. Yamada, H. Takahashi, S. Tsuji, J. Troncoso, V. L. Dawson, et al. Interference by Huntingtin and Atrophin-1 with CBP-Mediated Transcription Leading to Cellular Toxicity Science, March 23, 2001; 291(5512): 2423 - 2428. [Abstract] [Full Text]
|
|
|
|
|
|
S. Holbert, I. Denghien, T. Kiechle, A. Rosenblatt, C. Wellington, M. R. Hayden, R. L. Margolis, C. A. Ross, J. Dausset, R. J. Ferrante, et al. The Gln-Ala repeat transcriptional activator CA150 interacts with huntingtin: Neuropathologic and genetic evidence for a role in Huntington's disease pathogenesis PNAS, January 24, 2001; (2001) 41566798. [Abstract] [Full Text]
|
|
|
|
|
|
M. F. Beal and P. Hantraye Novel therapies in the search for a cure for Huntington's disease PNAS, January 2, 2001; 98(1): 3 - 4. [Full Text] [PDF]
|
|
|
|
|
|
A. Abel, J. Walcott, J. Woods, J. Duda, and D. E. Merry Expression of expanded repeat androgen receptor produces neurologic disease in transgenic mice Hum. Mol. Genet., January 1, 2001; 10(2): 107 - 116. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Trettel, D. Rigamonti, P. Hilditch-Maguire, V. C. Wheeler, A. H. Sharp, F. Persichetti, E. Cattaneo, and M. E. MacDonald Dominant phenotypes produced by the HD mutation in STHdhQ111 striatal cells Hum. Mol. Genet., November 1, 2000; 9(19): 2799 - 2809. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. F. Peters and C. A. Ross Isolation of a 40-kDa Huntingtin-associated Protein J. Biol. Chem., January 26, 2001; 276(5): 3188 - 3194. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Chai, L. Wu, J. D. Griffin, and H. L. Paulson The Role of Protein Composition in Specifying Nuclear Inclusion Formation in Polyglutamine Disease J. Biol. Chem., November 21, 2001; 276(48): 44889 - 44897. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Holbert, I. Denghien, T. Kiechle, A. Rosenblatt, C. Wellington, M. R. Hayden, R. L. Margolis, C. A. Ross, J. Dausset, R. J. Ferrante, et al. The Gln-Ala repeat transcriptional activator CA150 interacts with huntingtin: Neuropathologic and genetic evidence for a role in Huntington's disease pathogenesis PNAS, February 13, 2001; 98(4): 1811 - 1816. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. E. Hughes, R. S. Lo, C. Davis, A. D. Strand, C. L. Neal, J. M. Olson, and S. Fields Altered transcription in yeast expressing expanded polyglutamine PNAS, November 6, 2001; 98(23): 13201 - 13206. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. McCampbell, A. A. Taye, L. Whitty, E. Penney, J. S. Steffan, and K. H. Fischbeck Histone deacetylase inhibitors reduce polyglutamine toxicity PNAS, December 18, 2001; 98(26): 15179 - 15184. [Abstract] [Full Text] [PDF]
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