Hasan MK, Cheung C, Kaul Z, Shah N, Sakaushi S, Sugimoto K, Oka S, Kaul SC, Wadhwa R
CARF is a vital dual regulator of cellular senescence and apoptosis. [JOURNAL ARTICLE]
J Biol Chem 2008 Nov 10.
The tumor suppressor protein, p53, is central to the pathways that monitor the stress, DNA damage-repair, cell cycle, aging and cancer. Highly complex p53 networks involving its upstream sensors and regulators, downstream effectors and regulatory feedback loops have been identified. CARF (Collaborator of ARF) was shown to enhance ARF-dependent and -independent wild type p53 function. Here we report that (i) CARF overexpression causes premature senescence of human fibroblasts, (ii) it is vital for replicative and stress-induced senescence and (iii) the lack of CARF function causes aneuploidy and apoptosis. We provide evidence that CARF plays a dual role in regulating p53-mediated senescence and apoptosis, the two major tumor suppressor mechanisms.
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