Pharmacological and genetic perturbation establish SIRT5 as a promising target in breast cancer.

ABSTRACT: SIRT5 is a member of the sirtuin family of NAD⁺-dependent protein lysine deacylases implicated in a variety of physiological processes. SIRT5 removes negatively charged malonyl, succinyl, and glutaryl groups from lysine residues and thereby regulates multiple enzymes involved in cellular metabolism and other biological processes. SIRT5 is overexpressed in human breast cancers and other malignancies, but little is known about the therapeutic potential of SIRT5 inhibition for treating cancer. Here we report that genetic SIRT5 disruption in breast cancer cell lines and mouse models caused increased succinylation of IDH2 and other metabolic enzymes, increased oxidative stress, and impaired transformation and tumorigenesis. We, therefore, developed potent, selective, and cell-permeab

SUBMITTER: Abril YLN 

PROVIDER: S-EPMC7935767 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature