Oxygen-dependent asparagine hydroxylation of the ubiquitin-associated (UBA) domain in Cezanne regulates ubiquitin binding.

ABSTRACT: Deubiquitinases (DUBs) are vital for the regulation of ubiquitin signals, and both catalytic activity of and target recruitment by DUBs need to be tightly controlled. Here, we identify asparagine hydroxylation as a novel posttranslational modification involved in the regulation of Cezanne (also known as OTU domain-containing protein 7B (OTUD7B)), a DUB that controls key cellular functions and signaling pathways. We demonstrate that Cezanne is a substrate for factor inhibiting HIF1 (FIH1)- and oxygen-dependent asparagine hydroxylation. We found that FIH1 modifies Asn³⁵ within the uncharacterized N-terminal ubiquitin-associated (UBA)-like domain of Cezanne (UBA^Cez), which lacks conserved UBA domain properties. We show that UBA^Cez binds Lys¹¹-, Lys<

SUBMITTER: Mader J 

PROVIDER: S-EPMC7039550 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature