TY  - JOUR
A1  - Mader, Julia
A1  - Huber, Jessica
A1  - Bonn, Florian
A1  - Dötsch, Volker
A1  - Rogov, Vladimir V.
A1  - Bremm, Anja
T1  - Oxygen-dependent asparagine hydroxylation of the ubiquitin-associated (UBA) domain in Cezanne regulates ubiquitin binding
T2  - Journal of biological chemistry
N2  - 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 (UBACez), which lacks conserved UBA domain properties. We show that UBACez binds Lys11-, Lys48-, Lys63-, and Met1-linked ubiquitin chains in vitro, establishing UBACez as a functional ubiquitin-binding domain. Our findings also reveal that the interaction of UBACez with ubiquitin is mediated via a noncanonical surface and that hydroxylation of Asn35 inhibits ubiquitin binding. Recently, it has been suggested that Cezanne recruitment to specific target proteins depends on UBACez. Our results indicate that UBACez can indeed fulfill this role as regulatory domain by binding various ubiquitin chain types. They also uncover that this interaction with ubiquitin, and thus with modified substrates, can be modulated by oxygen-dependent asparagine hydroxylation, suggesting that Cezanne is regulated by oxygen levels.
KW  - deubiquitylation (deubiquitination)
KW  - ubiquitin
KW  - protein-protein interaction
KW  - nuclear magnetic resonance (NMR)
KW  - posttranslational modification (PTM)
KW  - Cezanne
KW  - FIH1
KW  - hydroxylation
KW  - UBA domain
KW  - deubiquitinase (DUB)
KW  - OTU domain-containing protein 7B (OTUD7B)
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/77675
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-776755
SN  - 0021-9258
VL  - 295.2020
IS  - 8
SP  - 2160
EP  - 2174
PB  - American Society for Biochemistry and Molecular Biology Publications
CY  - Bethesda, Md
ER  -