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.
ARF binding protein 1; ARF-binding protein 1; ARF-BP1; BJ-HCC-24 tumor antigen; E3 ubiquitin-protein ligase HUWE1; E3Histone; HECT domain protein LASU1; HECT, UBA and WWE domain-containing protein 1; HECT-type E3 ubiquitin transferase HUWE1; HectH9; Homologous to E6AP carboxyl terminus homologous protein 9; Large structure of UREB1; LASU1; Mcl-1 ubiquitin ligase; Mcl-1 ubiquitin ligase E3; Mule; RP3-339A18.4, ARF-BP1, HECTH9, HSPC272, Ib772, LASU1, MULE, UREB1; upstream regulatory element binding protein 1; Upstream regulatory element-binding protein 1; URE-B1; URE-binding protein 1