title: CARF Is a vital dual regulator of cellular senescence and apoptosis.
abstract: 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.
authors.affiliation: National Institute of Advanced Industrial Science & Technology (AIST), 1-1-1 Higashi, Tsukuba, Ibaraki 305-8562, Japan.
authors.forename: Kamrul
authors.initials: K
authors.lastname: Hasan
authors.forename: Caroline
authors.initials: C
authors.lastname: Cheung
authors.forename: Zeenia
authors.initials: Z
authors.lastname: Kaul
authors.forename: Navjot
authors.initials: N
authors.lastname: Shah
authors.forename: Shinji
authors.initials: S
authors.lastname: Sakaushi
authors.forename: Kenji
authors.initials: K
authors.lastname: Sugimoto
authors.forename: Shigenori
authors.initials: S
authors.lastname: Oka
authors.forename: Sunil C
authors.initials: SC
authors.lastname: Kaul
authors.forename: Renu
authors.initials: R
authors.lastname: Wadhwa
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D016922:Cellular Senescence / Q000502:physiology*; D004249:DNA Damage / Q000502:physiology; D004260:DNA Repair / Q000502:physiology; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D016601:RNA-Binding Proteins / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: D051017:Apoptosis Regulatory Proteins; C539004:CDKN2AIP protein, human; D016601:RNA-Binding Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53