CARF is a novel protein that cooperates with mouse p19ARF (human p14ARF in activating p53

Abstract

The INK4a locus on chromosome 9p21 encodes two structurally distinct tumor suppressor proteins, p16INK4α and the alternative reading frame protein, ARF (p19ARF in mouse and p14ARF in human). Each of these proteins has a role in senescence of primary cells and activates pathways for cell cycle control and tumor sup. pression. The current prevailing model proposes that p19ARF activates p53 function by antagonizing its degradation by MDM2. It was, however, recently shown that stabilization of p53 by p14ARF independent of the relocalization of MDM2 to the nucleolus. We have identified a novel collaborator of ARF, CARF. It co-localizes and interacts with ARF in the nucleolus. We demonstrate that CARF is co-regulated with ARF, cooperates with it in activating p53, and thus acts as a novel component of the ARF-p53-p21 pathway.