Type

Journal Article

Authors

Cormac T Taylor
Eoin P Cummins
Alex Von Kriegsheim
Roland H Wenger
Daniel J Peet
James A Nathan
Doug N Halligan
Bianca Crifo
Miguel A S Cavadas
Patrick Spielmann
and 6 others

Subjects

Biochemistry

Topics
metabolism cells cultured cellular response 1 protein hypoxia inducible factor hif cellular energy metabolism protein binding

FIH Regulates Cellular Metabolism through Hydroxylation of the Deubiquitinase OTUB1. (2015)

Abstract 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 FIH on N22. Mutation of N22 leads to a profound change in the interaction of OTUB1 with proteins important in cellular metabolism. Furthermore, in cultured cells, overexpression of N22A mutant OTUB1 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. Additionally, we propose that our results provide new insight into the regulation of cellular energy metabolism during hypoxic stress and the potential for targeting hydroxylases for therapeutic benefit.
Collections Ireland -> University College Dublin -> PubMed

Full list of authors on original publication

Cormac T Taylor, Eoin P Cummins, Alex Von Kriegsheim, Roland H Wenger, Daniel J Peet, James A Nathan, Doug N Halligan, Bianca Crifo, Miguel A S Cavadas, Patrick Spielmann and 6 others

Experts in our system

1
Cormac T. Taylor
University College Dublin
Total Publications: 110
 
2
Eoin P. Cummins
University College Dublin
Total Publications: 53
 
3
Alex Von Kriegsheim
University College Dublin
Total Publications: 19
 
4
Doug N Halligan
Dublin City University
Total Publications: 4
 
5
Bianca Crifo
University College Dublin
Total Publications: 5
 
6
Miguel A S Cavadas
University College Dublin
Total Publications: 13