The HACE1 E3 ligase mediates RAC1-dependent control of mTOR signaling complexes

ABSTRACT: HACE1 is a HECT family E3 ubiquitin-protein ligase with broad but incompletely understood tumor suppressor activity. Here we report a previously unrecognized link between HACE1 and signaling complexes containing mammalian target of rapamycin (mTOR). Specifically, HACE1 blocks mTORC1 and mTORC2 activities by reducing mTOR stability in an E3 ligase dependent manner. Mechanistically, HACE1 binds to and ubiquitylates Ras-related C3 botulinum toxin substrate 1 (RAC1) when RAC1 is associated with mTOR complexes, including at focal adhesions, leading to proteasomal degradation of RAC1. This in turn decreases stability of mTOR to reduce mTORC1 and mTORC2 activity. HACE1 deficient cells show enhanced mTORC1 activity, which is reversed by chemical or genetic RAC1 inactivation but not in cells expres

SUBMITTER: Busra Turgu 

PROVIDER: S-SCDT-10_15252-EMBR_202356815 | biostudies-other |

REPOSITORIES: biostudies-other