The activity and stability of the E3 ubiquitin ligase RING1B are controlled by the ubiquitin system. Self-ubiquitination of RING1B, generating K6, K27 and K48-based mixed polyubiquitin chains, is a prerequisite for its activity as an E3 ligase for histone H2A. Monoubiquitination of histone H2A is one of the hallmarks of Polycomb-mediated gene silencing. The destruction of RING1B however, is mediated through K48 polyubiquitination catalyzed by the ubiquitin ligase E6-AP. Both forms of ubiquitination of RING1B are mutually exclusive and therefore the balance between them may constitute a point of regulation of Polycomb-mediated gene repression. Here we identify ARF as a regulator of RING1B ubiquitination. ARF appears to selectively prevent RING1B self-ubiquitination, probably allowing more efficient E6-AP-mediated ubiquitination and subsequent degradation of RING1B. By binding to the RING domain of RING1B, ARF disrupts RING1B homodimerization, providing a potential mechanism for its effect on RING1B self-ubiquitination.