RING1B ubiquitination and stability are regulated by ARF.
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.
Cancer and Vascular Biology Research Center, The Rappaport Faculty of Medicine and Research Institute, Technion-Israel Institute of Technology, Haifa 31096, Israel. primdb@tx.technion.ac.il
Prim
P
de Bie
Aaron
A
Ciechanover
D002460:Cell Line; D006801:Humans; D063150:Polycomb Repressive Complex 1 / Q000737:chemistry*; D055503:Protein Multimerization; D055550:Protein Stability; D054829:RING Finger Domains; D016364:Reading Frames; D054875:Ubiquitination
D063150:Polycomb Repressive Complex 1; C489841:RNF2 protein, human