Lactate regulates cell cycle by remodelling the anaphase promoting complex.

ABSTRACT: Lactate is abundant in rapidly dividing cells owing to the requirement for elevated glucose catabolism to support proliferation^1-6. However, it is not known whether accumulated lactate affects the proliferative state. Here we use a systematic approach to determine lactate-dependent regulation of proteins across the human proteome. From these data, we identify a mechanism of cell cycle regulation whereby accumulated lactate remodels the anaphase promoting complex (APC/C). Remodelling of APC/C in this way is caused by direct inhibition of the SUMO protease SENP1 by lactate. We find that accumulated lactate binds and inhibits SENP1 by forming a complex with zinc in the SENP1 active site. SENP1 inhibition by lactate stabilizes SUMOylation of two residues on APC4, which drives UBE2C

SUBMITTER: Liu W 

PROVIDER: S-EPMC12175651 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature