BS69 is involved in cellular senescence through the p53-p21Cip1 pathway.
The multidomain-containing cellular protein BS69 interacts with adenovirus E1A and several other viral and cellular factors, and acts as a transcription repressor. Here, we show that BS69 is involved in the p53-p21Cip1-mediated senescence pathway. Knockdown of BS69 by RNA interference in human primary fibroblasts results in elevated levels of p21Cip1 and the appearance of several senescent markers, including enhanced senescence-associated beta-galactosidase activity and formation of senescence-associated heterochromatin foci. Importantly, knockdown of either p53 or p21Cip1, but not p16(INK4a) or Rb, allows cells to bypass premature senescence that is induced by BS69 knockdown. Furthermore, we show that BS69 forms complexes with both p53 and p400, and that BS69 associates with the p21Cip1 promoter through p53. Together, our data indicate that BS69 is involved in cellular senescence mainly through the p53-p21Cip1 pathway.
Zhang
Wei
W
Department of Biochemistry, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong.
Chan
Ho Man
HM
Gao
Yan
Y
Poon
Randy
R
Wu
Zhenguo
Z
D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology; D018797:Cell Cycle Proteins; D002460:Cell Line; D016922:Cellular Senescence / Q000235:genetics / Q000502:physiology*; D047369:Chromatin Immunoprecipitation; D056970:Co-Repressor Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins; D017353:Gene Deletion; D006367:HeLa Cells; D006801:Humans; D010957:Plasmids / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D056970:Co-Repressor Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004268:DNA-Binding Proteins; D034741:RNA, Small Interfering; D016159:Tumor Suppressor Protein p53; C094763:ZMYND11 protein, human