MCL1 modulates mTORC1 signaling to promote bioenergetics and tumorigenesis.

ABSTRACT: Myeloid cell leukemia-1 (MCL1) is among the most overexpressed proteins in tumors. MCL1 contributes to tumorigenesis by antagonizing apoptosis. However, apoptosis-unrelated functions are emerging. Screening an array of signaling switches identifies mTORC1 to be modulated by MCL1 but not by the anti-apoptotic Bcl-2 or Bcl-xL. mTORC1 is a central metabolic regulator. MCL1 impacts metabolism via modulating the expression of hexokinase 2 (HK2) in an mTORC1-dependent manner, which ultimately contributes to the tumor-promoting effects of MCL1. MCL1 inhibitors suppress mTORC1 in tumor cells but are associated with cardiotoxicity due to mTORC1 inhibition in the heart. Dietary leucine supplementation rescues mTORC1 signaling in the hearts of humanized Mcl-1 mice and greatly ameliorates the cardioto

SUBMITTER: Gui W 

PROVIDER: S-EPMC12673096 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature