CDKN2A Interacting Protein (CDKN2AIP)

CARF was first cloned as a novel binding partner of ARF from a yeast-interactive screen. CARF and ARF colocalize in the perinucleolar region and have a collaborative function. In the nucleoplasm, CARF interacts with p53 and enhances its function. p53 downregulates CARF in a negative feedback regulatory loop and may also involve p53 antagonist HDM2.

The INK4a locus on chromosome 9p21 encodes two structurally distinct tumor suppressor proteins, p16(INK4a) and the alternative reading frame protein, ARF (p19(ARF) in mouse and p14(ARF) in human). Each of these proteins has a role in senescence of primary cells and activates pathways for cell cycle control and tumor suppression. The current prevailing model proposes that p19(ARF) activates p53 function by antagonizing its degradation by MDM2.