biostudies-literatureUnknownGanga AKSwiss National Science FoundationNIGMS NIH HHSCentrosomes 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, <i>MAP3K1</i> knockout suppresses growth defects caused by <i>PPP2R3C</i> inactivation, and MAP3K1 and PPP2R3C have opposing effects on basal and microtubule stress-induced JNK signaling. Illustrating the importance of balabioRxiv : the preprint server for biology2024.04.02.587836https://www.ebi.ac.uk/biostudies/studies/S-EPMC11014585biostudies-literatureA disease-associated PPP2R3C-MAP3K1 phospho-regulatory module controls centrosome function.PMC11014585R35 GM137956205087310030Ganga AKRamos ARSweeney LKBishop CSHamel VBreslow DKGuichard PfalseA disease-associated PPP2R3C-MAP3K1 phospho-regulatory module controls centrosome function.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, <i>MAP3K1</i> knockout suppresses growth defects caused by <i>PPP2R3C</i> inactivation, and MAP3K1 and PPP2R3C have opposing effects on basal and microtubule stress-induced JNK signaling. Illustrating the importance of bala2024-01-01T00:00:00Z2024 Apr2026-05-18T03:13:31.259Z2026-05-18T03:07:35.384ZS-EPMC110145853861727010.1101/2024.04.02.587836