SIRT2-dependent IDH1 deacetylation inhibits colorectal cancer and liver metastases.

ABSTRACT: Protein lysine acetylation affects colorectal cancer (CRC) distant metastasis through multiple pathways. In a previous proteomics screen, we found that isocitrate dehydrogenase 1 (IDH1) is hyperacetylated in CRC primary tumors and liver metastases. Here, we further investigate the function of IDH1 hyperacetylation at lysine 224 in CRC progression. We find that IDH1 K224 deacetylation promotes its enzymatic activity and the production of α-KG, and we identify sirtuin-2 (SIRT2) as a major deacetylase for IDH1. SIRT2 overexpression significantly inhibits CRC cell proliferation, migration, and invasion. IDH1 acetylation is modulated in response to intracellular metabolite concentration and regulates cellular redox hemostasis. Moreover, IDH1 acetylation reversely regulates HIF1α-dependent SRC t

SUBMITTER: Wang B 

PROVIDER: S-EPMC7132198 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature