The p400 E1A-associated protein is a novel component of the p53 --> p21 senescence pathway.
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.
Chan
Ho Man
HM
Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
Narita
Masako
M
Lowe
Scott W
SW
Livingston
David M
DM
D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000235:genetics / Q000502:physiology*; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005347:Fibroblasts / Q000502:physiology; D016193:G1 Phase / Q000235:genetics / Q000502:physiology; D006801:Humans; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic / Q000235:genetics / Q000502:physiology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
C493956:CDKN1A protein, human; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D016159:Tumor Suppressor Protein p53; D004265:DNA Helicases; C498558:EP400 protein, human