The ARF tumor suppressor is a critical regulator of p53 stability.  In addition to p53, ARF1 binds to other proteins such as MDM2 and ARF-BP1, a large protein containing HECT, UBA and WWE motifs.  ARF-BP1 directly binds and ubiquitinates p53; this activity is inhibited by ARF, indicating that ARF-BP1 is a critical mediator of the p53-dependent and p53-independent tumor suppressor functions of ARF.  ARF-BP1 can also catalyze the polyubiquitination of Mcl-1, an anti-apoptotic Bcl-2 family member involved in DNA damage-induced apoptosis.  Elimination of ARF-BP1 expression by RNA interference stabilized Mcl-1 protein, resulting in an attenuation of apoptosis induced by DNA-damage agents.