Cellular senescence represents a permanent withdraw from cell cycle in response to diverse stress; it is controlled by the p53 and retinoblastoma protein (RB) tumor suppressors, and constitutes a potent anticancer mechanisms. p53 can be deacetylated by a protein complex containing histone deacetylases (HDAC1).
The Rb tumor suppressor gene performs a critical role in controlling cell proliferation and tumorigenesis; it recruits HDAC1 protein into the E2F complexes to repress transcription.
These results provide new insights into the role of the RB pathway in regulating cellular senescence and implicate HDAC1 as a likely mediator of early chromatin remodeling events.
Following the subcloning of the promoter regions into a gene reporter system, we found that at least four promoter haplotypes associated with CCND1, E2F1, HDAC1 and RB1 significantly influenced transcriptional activity in an allele-specific manner.