| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Papers In Press, published online ahead of print October 31, 2005
Institute of Molecular and Cellular Biosciences, University of Tokyo, Bunkyo-ku, Tokyo 113-0032
Corresponding Author: uskato{at}mail.ecc.u-tokyo.ac.jp
It is well established that genetic mutations that impair BRCA1 function predispose women to early onset of breast and ovarian cancer (1,2). However, the co-regulatory factors that support normal BRCA1 functions remain to be identified. Using a biochemical approach to search for such co-regulatory factors, we identified hGCN5, TRRAP, and hMSH2/6 as BRCA1-interacting proteins. Genetic mutations in the C-terminal transactivation domain of BRCA1, as found in breast cancer patients (3), caused the loss of physical interaction between BRCA1 and TRRAP, and significantly reduced the co-activation of BRCA1 transactivation function by hGCN5/TRRAP. The reported transcriptional squelching between BRCA1 and estrogen receptor a (4) was rescued by the overexpression of TRRAP or hGCN5. Histone acetyltransferase hGCN5 activity appeared to be indispensable for co-regulator complex function in both BRCA1-mediated gene regulation and DNA repair. Biochemical purification of the hGCN5/TRRAP-containing complex suggested that hGCN5/TRRAP formed a complex with hMSH2/hMSH6, presumably as a novel subclass of hGCN5/TRRAP-containing known TFTC (TBP-free TAFII-containing)-type HAT complex (hTFTC, hPCAF, and hSTAGA) (5-7). Unlike other subclasses, the isolated complex harbored a previously unknown combination of components including hMSH2 and hMSH6, major components of the BRCA1 genome surveillance repair complex (BASC). Thus, our results suggested that the multiple BRCA1 functions require a novel hGCN5/TRRAP HAT complex subclass.
J. Biol. Chem, 10.1074/jbc.M510157200
Submitted on September 15, 2005
Accepted on October 31, 2005
An hGCN5/TRRAP HAT complex coactivates BRCA1 transactivation function through histone modification
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  M. A. Park, Y.-J. Seok, G. Jeong, and J.-S. Lee SUMO1 negatively regulates BRCA1-mediated transcription, via modulation of promoter occupancy Nucleic Acids Res., January 17, 2008; 36(1): 263 - 283. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Liu, M. Vorontchikhina, Y.-L. Wang, F. Faiola, and E. Martinez STAGA Recruits Mediator to the MYC Oncoprotein To Stimulate Transcription and Cell Proliferation Mol. Cell. Biol., January 1, 2008; 28(1): 108 - 121. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. DeRan, M. Pulvino, E. Greene, C. Su, and J. Zhao Transcriptional Activation of Histone Genes Requires NPAT-Dependent Recruitment of TRRAP-Tip60 Complex to Histone Promoters during the G1/S Phase Transition Mol. Cell. Biol., January 1, 2008; 28(1): 435 - 447. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G.-H. Peng and S. Chen Crx activates opsin transcription by recruiting HAT-containing co-activators and promoting histone acetylation Hum. Mol. Genet., October 15, 2007; 16(20): 2433 - 2452. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |
