Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P62988 (Ubiquitin)
 4,326 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The E3 ubiquitin ligase RING1B plays an important role in Polycomb-mediated gene silencing by monoubiquitinating histone H2A. Both the activity and stability of RING1B are controlled by ubiquitination in two distinct manners. Self ubiquitination of RING1B generates K6, K27 and K48-based mixed polyubiquitin chain, and is required for its activity as a ligase. On the other hand, its proteasomal degradation is mediated by another ligase; E6-AP catalyzes the formation of K48-based chains. Since these two modes of ubiquitination target the same lysine residues and are therefore mutually exclusive, an important mode of regulation of RING1B should be at the level of deubiquitination. Here we identify USP7 as a deubiquitinating enzyme that regulates the ubiquitination state of RING1B. RING1B interacts with USP7, which is mediated in part by its RING domain. In addition, USP7 was found in a complex with other Polycomb proteins, suggesting a broad role in regulating these complexes. Although, USP7 directly and specifically deubiquitinates RING1B in vitro and in vivo, it does not discriminate between the activating and proteolysis-targeting modes of ubiquitination, and therefore has a stabilizing effect on RING1B.
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PMID:Regulation of the Polycomb protein RING1B ubiquitination by USP7. 2080 May 74

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.
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PMID:RING1B ubiquitination and stability are regulated by ARF. 2291 Apr 19