LIMK2 promotes centrosome clustering and cancer progression by activating MST4-mediated phosphorylation of NPM1.

ABSTRACT: Centrosome amplification, a hallmark of diverse malignancies, enables cancer cell survival through centrosome clustering during mitosis, presenting a promising therapeutic target for selective elimination of cancer cells with supernumerary centrosomes. While the regulatory mechanisms underlying centrosome clustering remain poorly understood, our study identifies LIM kinase 2 (LIMK2) as a critical regulator of this process, demonstrating cancer correlation with tumor progression. Mechanistically, LIMK2 phosphorylates mammalian sterile-20-like kinase 4 (MST4) at threonine 178 (T178), activating its kinase function. Activated MST4 subsequently binds and phosphorylates nucleophosmin 1 (NPM1) at T95, a modification essential for centrosome clustering and tumor cell proliferation. Genetic deplet

SUBMITTER: Tian J 

PROVIDER: S-EPMC12436196 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature