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

Centrosomes have critical roles in microtubule organization, ciliogenesis, and cell signaling. Centrosomal alterations also contribute to diseases, including microcephaly, cancer, and ciliopathies. To date, over 150 centrosomal proteins have been identified, including several kinases and phosphatases that control centrosome biogenesis, function, and maintenance.

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

Centrosomes have critical roles in microtubule organization and in cell signaling. 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.

Abemaciclib Is Effective in Palbociclib-Resistant Hormone Receptor-Positive Metastatic Breast Cancers.

Unlabelled: Cyclin-dependent kinases 4/6 inhibitor (CDK4/6i) plus endocrine therapy (ET) is standard of care for patients with hormone receptor (HR)-positive, HER2-negative metastatic breast cancer (MBC). However, resistance to CDK4/6is plus ET remains a clinical problem with limited therapeutic options following disease progression. Different CDK4/6is might have distinct mechanisms of resistance, and therefore using them sequentially or targeting their differentially altered pathways could delay disease progression.