Specific CP110 Phosphorylation Sites Mediate Anaphase Catastrophe after CDK2 Inhibition: Evidence for Cooperation with USP33 Knockdown.

ABSTRACT: Chromosomal instability (CIN) is a hallmark of solid tumor biology and is implicated in carcinogenesis. Preferentially eliminating malignant cells by targeting CIN and aneuploidy is an attractive antineoplastic strategy. We previously reported that CDK2 antagonism causes lung cancer cells to undergo anaphase catastrophe and apoptosis through inhibition of phosphorylation of the centrosomal protein CP110. Cells with activating KRAS mutations were particularly sensitive to CDK2 inhibition due to downregulation of CP110 protein levels. This study investigated mechanisms of CDK2 antagonism that mediate anaphase catastrophe via changes in CP110 protein expression and how activated KRAS affects CP110 levels in lung cancers. Site-directed mutagenesis revealed candidate CDK phosphorylation sites o

SUBMITTER: Hu S 

PROVIDER: S-EPMC4636444 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature