Skip Navigation


Human Molecular Genetics Advance Access originally published online on December 22, 2006
Human Molecular Genetics 2007 16(2):199-209; doi:10.1093/hmg/ddl464
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
16/2/199    most recent
ddl464v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (10)
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Schneikert, J.
Right arrow Articles by Behrens, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Schneikert, J.
Right arrow Articles by Behrens, J.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2006. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Truncated APC regulates the transcriptional activity of ß-catenin in a cell cycle dependent manner

Jean Schneikert*, Annette Grohmann and Jürgen Behrens

Nikolaus-Fiebiger-Center for Molecular Medicine, University Erlangen-Nürnberg, Glückstrasse 6, 91054 Erlangen, Germany

* To whom correspondence should be addressed. Tel: +49 91318529110; Fax: +49 91318529111; Email: jschneik{at}molmed.uni-erlangen.de

Received October 9, 2006; Revised November 28, 2006; Accepted December 8, 2006

Most colon cancer cells express truncated versions of the tumour suppressor Adenomatous Polyposis Coli (APC). These molecules are selected during tumourigenesis for impaired ß-catenin degrading activity. In this study, we describe that truncated APC can still control the activity of ß-catenin in colon cancer cell lines via its first 20 amino acid repeat. First, we show that both endogenous and ectopically expressed truncated APC molecules can bind to ß-catenin. Second, reduction of the levels of truncated APC by RNA interference increases the activity of a ß-catenin-dependent reporter gene and stimulates the expression of the ß-catenin target gene AXIN2/conductin. This occurs without alterations of the amounts of cytosolic ß-catenin. Conversely, ectopic expression of truncated APC decreases ß-catenin-dependent transcription without affecting the intensity of immunofluorescence staining of ß-catenin in transfected cells. Third, we reveal that the APC level increases when cells reach the G1-S boundary during cell cycle progression. Simultaneously, the amount of ß-catenin bound to APC increases and the transcriptional activity of ß-catenin drops in an APC-dependent manner. Again, this occurs independently of the amounts of either total or phosphorylated cytosolic ß-catenin. Together, these results indicate that truncated APC controls the ability of ß-catenin to activate transcription. As we also show that the inhibition involves the first 20 amino acid repeat of APC, our data suggest that colon cancer cells retain a truncated APC molecule containing at least the first 20 amino acid repeat to modulate the transcriptional activity of ß-catenin in a cell cycle-dependent manner.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Hum Mol GenetHome page
E. M. Kohler, S. H. V. Chandra, J. Behrens, and J. Schneikert
{beta}-Catenin degradation mediated by the CID domain of APC provides a model for the selection of APC mutations in colorectal, desmoid and duodenal tumours
Hum. Mol. Genet., January 15, 2009; 18(2): 213 - 226.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
E. M. Kohler, A. Derungs, G. Daum, J. Behrens, and J. Schneikert
Functional definition of the mutation cluster region of adenomatous polyposis coli in colorectal tumours
Hum. Mol. Genet., July 1, 2008; 17(13): 1978 - 1987.
[Abstract] [Full Text] [PDF]

Home page
 GENES CELLSHome page
A. P. Kouzmenko, K.-i. Takeyama, Y. Kawasaki, T. Akiyama, and S. Kato
Ligand-dependent interaction between estrogen receptor alpha and adenomatous polyposis coli.
Genes Cells, July 1, 2008; 13(7): 723 - 730.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
M. Brocardo, Y. Lei, A. Tighe, S. S. Taylor, M. T. S. Mok, and B. R. Henderson
Mitochondrial Targeting of Adenomatous Polyposis Coli Protein Is Stimulated by Truncating Cancer Mutations: REGULATION OF Bcl-2 AND IMPLICATIONS FOR CELL SURVIVAL
J. Biol. Chem., February 29, 2008; 283(9): 5950 - 5959.
[Abstract] [Full Text] [PDF]

Home page
 ScienceHome page
C. M. Takacs, J. R. Baird, E. G. Hughes, S. S. Kent, H. Benchabane, R. Paik, and Y. Ahmed
Dual Positive and Negative Regulation of Wingless Signaling by Adenomatous Polyposis Coli
Science, January 18, 2008; 319(5861): 333 - 336.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
A. L. Eisinger, L. D. Nadauld, D. N. Shelton, S. M. Prescott, D. M. Stafforini, and D. A. Jones
Retinoic Acid Inhibits beta-Catenin through Suppression of Cox-2: A ROLE FOR TRUNCATED ADENOMATOUS POLYPOSIS COLI
J. Biol. Chem., October 5, 2007; 282(40): 29394 - 29400.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.