Abstract
KLF11 is a biochemical paradigm for a subset of proteins that repress transcription via a Mad1-like mSin3A interacting domain (SID). The biological role of these proteins and the significance of their biochemical activity, however, remain to be established. We report that KLF11 is downregulated in human cancers, inhibits cell growth in vitro and in vivo, and suppresses neoplastic transformation. Transgenic mice for KLF11 display a downregulation of genes encoding the oxidative stress scavengers SOD2 and Catalase1. Chromatin immunoprecipitation assays confirm that, indeed, these genes are bonafide targets of KLF11. KLF11 expression renders cells more sensitive to oxidative drugs, an effect that is rescued by infection with recombinant adenoviruses expressing SOD2 and Catalasel. KLF11-regulated functions require the Mad1-like SID, indicating that these target genes involved in these phenomena are regulated via this corepressor system. These results demonstrate that SID-containing KLF repressor proteins can inhibit cell growth and neoplastic transformation, and outline for the first time cellular and molecular mechanisms by which these functions may be achieved.
Original language | English (US) |
---|---|
Pages (from-to) | 4748-4758 |
Number of pages | 11 |
Journal | EMBO Journal |
Volume | 22 |
Issue number | 18 |
DOIs | |
State | Published - Sep 15 2003 |
Keywords
- Apoptosis
- Cell growth
- KLF11
- SID
- mSin3A
ASJC Scopus subject areas
- General Neuroscience
- Molecular Biology
- General Biochemistry, Genetics and Molecular Biology
- General Immunology and Microbiology