MassIVE MSV000080695

Partial Public PXD002103

FIH regulates cellular metabolism through hydroxylation of the deubiquitinase OTUB1.

Description

The asparagine hydroxylase, factor inhibiting HIF (FIH) confers oxygen-dependence upon the hypoxia-inducible factor (HIF), a master regulator of the cellular adaptive response to hypoxia. Studies investigating whether asparagine hydroxylation is a general regulatory oxygen-dependent modification have identified multiple non-HIF targets for FIH. However the functional consequences of this outside of the HIF pathway remain unclear. Here, we demonstrate that the deubiquitinase ovarian tumor domain containing, ubiquitin aldehyde binding protein 1 (OTUB1) is a substrate for hydroxylation by endogenous FIH on N22. Mutation of N22 leads to a profound change in the interaction of OTUB1 with proteins important in cellular metabolism. Furthermore, mutant OTUB1 (lacking the hydroxylation site) impairs cellular metabolic processes when compared to wild type. Based on these data, we hypothesize that OTUB1 is a target for functional hydroxylation by FIH, and propose that this provides new insight into the regulation of cellular energy metabolism during hypoxia. [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: Hydroxylase ; hypoxia ; metabolism ; ubiquitin ; deubiquitinating enzyme.

Contact

Principal Investigators: Cormac Taylar, Principal Investigator. SBI (System Biology Ireland), Conway Institute, UCD, N/A
Submitting User: ccms

Publications

Scholz CC, Rodriguez J, Pickel C, Burr S, Fabrizio JA, Nolan KA, Spielmann P, Cavadas MA, Crifo B, Halligan DN, Nathan JA, Peet DJ, Wenger RH, Von Kriegsheim A, Cummins EP, Taylor CT.
FIH Regulates Cellular Metabolism through Hydroxylation of the Deubiquitinase OTUB1.
PLoS Biol. 2016 Jan;14(1):e1002347. Epub 2016 Jan 11.

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