Work

DUBs, Hypoxia, and Cancer

Year: 2019

Type: review

Abstract: 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.

Source: Trends in cancer

DOI: 10.1016/j.trecan.2019.08.005

Authors: Daniela Mennerich, Kateryna Kubaichuk, Thomas Kietzmann

Institution: University of Oulu

Language: English

Topic: Ubiquitin and proteasome pathways

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $4,000