A disease-associated PPP2R3C-MAP3K1 phospho-regulatory module controls centrosome function.

ABSTRACT: Centrosomes have critical roles in microtubule organization and in cell signaling.^1-8 However, the mechanisms that regulate centrosome function are not fully defined, and thus how defects in centrosomal regulation contribute to disease is incompletely understood. From functional genomic analyses, we find here that PPP2R3C, a PP2A phosphatase subunit, is a distal centriole protein and functional partner of centriolar proteins CEP350 and FOP. We further show that a key function of PPP2R3C is to counteract the kinase activity of MAP3K1. In support of this model, MAP3K1 knockout suppresses growth defects caused by PPP2R3C inactivation, and MAP3K1 and PPP2R3C have opposing effects on basal and microtubule stress-induced JNK signaling. Illustrating the importance of bala

SUBMITTER: Ganga AK 

PROVIDER: S-EPMC11014585 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature