Human Molecular Genetics, Vol 7, 371-378, Copyright © 1998 by Oxford University Press
JM Boutell, JD Wood, PS Harper and AL Jones
We have screened a rat brain library to identify proteins which interact
with the 5'-end of huntingtin (amino acids 1-171), including the
polyglutamine tract, in the yeast two-hybrid system. We detected an
interaction with cystathionine beta-synthase (CBS) [L-serine hydrolyase
(adding homocysteine), EC 4.2.1.22], which was confirmed in vitro using
His-tagged CBS expressed in Escherichia coli , which was able to
specifically bind both rat and human full-length huntingtin. Neither normal
nor expanded polyglutamine repeat alone interacted with CBS in the yeast
two-hybrid system and nor did constructs containing SBMA or DRPLA with
normal or expanded polyglutamine tracts. CBS therefore appears to bind
specifically to huntingtin. CBS deficiency is associated with
homocystinuria, which is known to affect various physiological systems,
including the central nervous system. Homocysteine, one of the substrates
of CBS, is known to accumulate in homocystinuria and is metabolized to
homocysteate and homocysteine sulphinate, both known to be powerful
excitotoxic amino acids. It has been suggested that Huntington's disease
involves the action of excitotoxic amino acids and this interaction with
CBS may suggest a mechanism for such excitotoxic damage.
ARTICLES
Huntingtin interacts with cystathionine beta-synthase
Institute of Medical Genetics, University of Wales College of Medicine, Cardiff CF4 4XN, UK.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  C. M. Everett and N. W. Wood Trinucleotide repeats and neurodegenerative disease Brain, November 1, 2004; 127(11): 2385 - 2405. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. R. Singaraja, S. Hadano, M. Metzler, S. Givan, C. L. Wellington, S. Warby, A. Yanai, C.-A. Gutekunst, B. R. Leavitt, H. Yi, et al. HIP14, a novel ankyrin domain-containing protein, links huntingtin to intracellular trafficking and endocytosis Hum. Mol. Genet., November 1, 2002; 11(23): 2815 - 2828. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. P. Mattson, S. L. Chan, and W. Duan Modification of Brain Aging and Neurodegenerative Disorders by Genes, Diet, and Behavior Physiol Rev, July 1, 2002; 82(3): 637 - 672. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. A. Passani, M. T. Bedford, P. W. Faber, K. M. McGinnis, A. H. Sharp, J. F. Gusella, J.-P. Vonsattel, and M. E. MacDonald Huntingtin's WW domain partners in Huntington's disease post-mortem brain fulfill genetic criteria for direct involvement in Huntington's disease pathogenesis Hum. Mol. Genet., September 1, 2000; 9(14): 2175 - 2182. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. D. Davidson, B. Riley, E. N. Burright, L. A. Duvick, H. Y. Zoghbi, and H. T. Orr Identification and characterization of an ataxin-1-interacting protein: A1Up, a ubiquitin-like nuclear protein Hum. Mol. Genet., September 1, 2000; 9(15): 2305 - 2312. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Shibata, D. P. Huynh, and S.-M. Pulst A novel protein with RNA-binding motifs interacts with ataxin-2 Hum. Mol. Genet., May 22, 2000; 9(9): 1303 - 1313. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Krobitsch and S. Lindquist Aggregation of huntingtin in yeast varies with the length of the polyglutamine expansion and the expression of chaperone proteins PNAS, February 15, 2000; 97(4): 1589 - 1594. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Boutell, P. Thomas, J. W. Neal, V. J. Weston, J. Duce, P. S. Harper, and A. L. Jones Aberrant interactions of transcriptional repressor proteins with the Huntington's disease gene product, huntingtin Hum. Mol. Genet., September 1, 1999; 8(9): 1647 - 1655. [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]
|
|