CARF is a multi-module regulator of cell proliferation and a molecular bridge between cellular senescence and carcinogenesis.
CARF (Collaborator of ARF) was first identified as an ARF (Alternative Reading Frame, p14ARF)-interacting protein in a yeast two-hybrid interactive screening. Subsequently, it was shown to stabilize the p53-tumor suppressor protein in an ARF-dependent or -independent manner. It acts as a transcriptional repressor of HDM2 that exerts a negative feedback on p53 by its proteasomal-mediated degradation. CARF-driven control over p53-HDM2-p21WAF1 axis was shown to regulate cell proliferative fates. Cells with CARF-overexpression (CARF-OE) and superexpression (CARF-SE) showed growth arrest and pro-proliferative phenotypes, respectively. On the other hand, apoptosis was triggered in CARF-compromised cells. In the present review, we provide a comprehensive current understanding into the molecular mechanisms of CARF functions in regulation of DNA damage response, cell cycle checkpoints, cell survival and death signaling pathways. We discuss how thresh-hold of CARF level determines fate of cells to senescence and malignant transformation.
['Wadhwa|Renu|R|', 'Kalra|Rajkumar Singh|RS|', 'Kaul|Sunil C|SC|']
D000818:Animals D051017:Apoptosis Regulatory Proteins D059447:Cell Cycle Checkpoints D002471:Cell Transformation, Neoplastic D016922:Cellular Senescence D050759:Cyclin-Dependent Kinase Inhibitor p21 D004249:DNA Damage D006801:Humans D051736:Proto-Oncogene Proteins c-mdm2 D016601:RNA-Binding Proteins D025803:Tumor Suppressor Protein p14ARF D016159:Tumor Suppressor Protein p53
CARF Senescence Superexpression Malignant transformation Overexpression