Work

The p400 E1A-associated protein is a novel component of the p53 → p21 senescence pathway

Year: 2005

Type: preprint

Abstract: Adenovirus E1A-associated p400 belongs to the SWI2/SNF2 family of chromatin remodeling proteins. Here, we report that p400 is a component of the p53-p21(WAF1/CIP1/sid1) pathway, regulating the p21 transcription and senescence induction program. Acute depletion of p400 expression by shRNA (short hairpin RNA) synthesis led to premature senescence of untransformed human fibroblasts, whose features include G1 arrest, p21 induction, senescence-associated heterochromatic foci (SAHF), and beta-gal staining. Importantly, p400shRNA-induced premature senescence phenotypes were rescued by coexpression of p53-shRNA or p21-shRNA. Furthermore, p400 complex colocalized with p53 on the p21 promoter. These data suggest that the p400 complex inhibits p53 --> p21 transcription and the development of premature senescence.

Source: Genes & Development

DOI: 10.1101/gad.1280205

Authors: Ho Man Chan, Masako Narita, Scott W. Lowe, David M. Livingston

Institutions: Harvard University, Dana-Farber Cancer Institute, Cold Spring Harbor Laboratory, Dana-Farber/Harvard Cancer Center

Language: English

Topic: Telomeres, Telomerase, and Senescence

Subfield: Physiology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: diamond

Funder: National Cancer Institute