The Role of N-CoR During Normal Mammary Gland Development
Abstract
Understanding the regulation of N-CoR and its associated corepressors, in concert with defining the molecular mechanisms that underlie regulation by estrogen- receptor, offers a reasonable prospect of achieving new approaches to diagnosis and treatment of breast cancer. Here, we demonstrated that estrogen receptor recruits at least two distinct N-CoR-containing complexes as mSin3/HDAC 2/1 and also the novel TAB2/HDAC3/N-CoR complex that bind to antagonist. Also, we identification of a novel N-CoR complex containing a factor TAB2 and HDAC3 as a nuclear repressor complex. The inflammatory signals such as IL- lb causes export of the TAB2/N-CoR/HDAC3 complex from nucleus to cytoplasm by MEKK1 action. Furthermore, our results revealed that a specific complex such as TBL1/TBLR1 is required for activation of ER(alpha), based on its function in antagonizing N-CoR/SMRT by ubiquitin ligase mediated exchange for transcriptional activation. Among the N-CoR corepressor target genes, c-myc and KA1 plays important roles in the cell cycle control and metastases during breast cancer. In this report, we suggested that N-CoR is linked to Beta-catenin signaling pathway and N-CoR/TAB2 might be involved in the regulation of the expression of an important metastasis suppressor gene.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2003
- Accession Number
- ADA418738
Entities
People
- Bong-gun Ju
- Michael G. Rosenfeld
Organizations
- University of California, San Diego