USP33 Deubiquitinates and Stabilizes HIF-2alpha to Promote Hypoxia Response in Glioma Stem Cells

ABSTRACT: Hypoxia regulates tumor angiogenesis, metabolism, and therapeutic response in malignant cancers including glioblastoma, the most lethal primary brain tumor. The regulation of HIF transcriptional factors by the ubiquitin-proteasome system is critical in the hypoxia response, but hypoxia-inducible deubiquitinases that counteract the ubiquitination remain poorly defined. While the activation of ERK1/2 also plays an important role in hypoxia response, the relationship between ERK1/2 activation and HIF regulation remains elusive. Here, we identified USP33 as essential deubiquitinase that stabilizes HIF-2alpha protein in an ERK1/2-dependent manner to promote hypoxia response in cancer cells. USP33 is preferentially induced in glioma stem cells by hypoxia and interacts with HIF-2alpha, leading to

SUBMITTER: Dr. Aili Zhang 

PROVIDER: S-SCDT-EMBOJ-2021-109187 | biostudies-other |

REPOSITORIES: biostudies-other