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- Title
p53 and its homologues, p63 and p73, induce a replicative senescence through inactivation of NF-Y transcription factor.
- Authors
Jung, Mun-Su; Yun, Jeanho; Chae, Hee-Don; Kim, Jeong-Min; Kim, Sun-Chang; Choi, Tae-Saeng; Shin, Deug Y
- Abstract
Recent studies have identified two p53 homologues, p63 and p73. They activate p53-responsive promoters and induce apoptosis when overexpressed in certain human tumors. Here, we report that p63, like p53 and p73, induces replicative senescence when expressed in a tetracycline-regulated manner in EJ cells lacking a functional p53. In addition to transcription activation of p53-responsive genes, we found that p63 and p73 repress transcription of the cdk1 and cyclin B genes, both of which are irreversibly repressed in senescent human fibroblast. In transient transfection assay, p63 and p73 repress the cdk1 promoter regardless of the presence of a dominant negative mutant form of p53. Furthermore, we found that DNA binding activity of NF-Y transcription factor, which is essential for transcription of the cdk1 and cyclin B genes and inactivated in senescent fibroblast, is significantly decreased by expression of either of p53, p63, or p73. Since NF-Y binds to many promoters besides the cdk1 and cyclin B promoters, inactivation of NF-Y by p53 family genes may be a general mechanism for transcription repression in replicative senescence. Oncogene (2001) 20, 5818–5825.
- Subjects
GENES; P53 antioncogene; TETRACYCLINE
- Publication
Oncogene, 2001, Vol 20, Issue 41, p5818
- ISSN
0950-9232
- Publication type
Article
- DOI
10.1038/sj.onc.1204748