EMAIL THIS PAGE TO A FRIEND

Biochemical and biophysical research communications

RING1B ubiquitination and stability are regulated by ARF.


PMID 22910419

Abstract

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.