Proteome dynamics analysis identifies functional roles of SDE2 and hypoxia in DNA damage response in prostate cancer cells.

ABSTRACT: Mechanistic understanding of hypoxia-responsive signaling pathways provides important insights into oxygen- and metabolism-dependent cellular phenotypes in diseases. Using SILAC-based quantitative proteomics, we provided a quantitative map identifying over 6300 protein groups in response to hypoxia in prostate cancer cells and identified both canonical and novel cellular networks dynamically regulated under hypoxia. Particularly, we identified SDE2, a DNA stress response modulator, that was significantly downregulated by hypoxia, independent of HIF (hypoxia-inducible factor) transcriptional activity. Mechanistically, hypoxia treatment promoted SDE2 polyubiquitination and degradation. Such regulation is independent of previously identified Arg/N-end rule proteolysis or the ubiquitin E3 liga

SUBMITTER: Luo A 

PROVIDER: S-EPMC7380487 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature