University of Oulu

Daniela Mennerich, Kateryna Kubaichuk, Thomas Kietzmann, DUBs, Hypoxia, and Cancer, Trends in Cancer, Volume 5, Issue 10, 2019, Pages 632-653, ISSN 2405-8033,

DUBs, hypoxia, and cancer

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Author: Mennerich, Daniela1; Kubaichuk, Kateryna1; Kietzmann, Thomas1,2
Organizations: 1Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, 90570, Finland
2Biocenter Oulu, University of Oulu, Oulu, 90570, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 2.9 MB)
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Language: English
Published: Elsevier, 2019
Publish Date: 2020-02-24


Alterations in protein ubiquitylation and hypoxia are commonly associated with cancer. Ubiquitylation is carried out by three sequentially acting ubiquitylating enzymes and can be opposed by deubiquitinases (DUBs), which have emerged as promising drug targets. Apart from protein localization and activity, ubiquitylation regulates degradation of proteins, among them hypoxia-inducible factors (HIFs). Thereby, various E3 ubiquitin ligases and DUBs regulate HIF abundance. Conversely, several E3s and DUBs are regulated by hypoxia. While hypoxia is a powerful HIF regulator, less is known about hypoxia-regulated DUBs and their impact on HIFs. Here, we review current knowledge about the relationship of E3s, DUBs, and hypoxia signaling. We also discuss the reciprocal regulation of DUBs by hypoxia and use of DUB-specific drugs in cancer.

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Series: Trends in cancer
ISSN: 2405-8033
ISSN-E: 2405-8025
ISSN-L: 2405-8033
Volume: 5
Issue: 10
Pages: 632 - 653
DOI: 10.1016/j.trecan.2019.08.005
Type of Publication: A2 Review article in a scientific journal
Field of Science: 1182 Biochemistry, cell and molecular biology
3122 Cancers
Funding: The work in the authors’ laboratory was supported by grants from the Finnish Center of International Mobility, Finnish Academy of Sciences (SA296027), Jane and Aatos Erkko Foundation, Finnish Cancer Foundation, Sigrid Juselius Foundation, Biocenter Oulu, and University of Oulu.
Academy of Finland Grant Number: 296027
Detailed Information: 296027 (Academy of Finland Funding decision)
Copyright information: © 2019 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license ( in Cancer