Oncoprotein 18 is a phosphorylation-responsive regulator of microtubule dynamics

Oncoprotein 18 (Op18, also termed p19, p18, prosolin or stathmin) is a cytosolic protein of previously unknown function. Phosphorylation of Op18 is cell cycle regulated by cyclin-dependent kinases (CDKs), and expression of a 'CDK target site-deficient mutant' results in a phenotype indicative of a role for Op18 during mitosis, This phenotype is compatible with the idea that Op18 is a phosphorylation-responsive regulator of microtubule (MT) dynamics, Therefore, in this study, we analyzed MTs in cells induced to express either wild-type or mutated Op18, The results showed that wild-type Op18 and a CDK target site mutant both efficiently elicited rapid depolymerization of MTs, This result contrasts with clear-cut differences in their cell cycle phenotypes, Morphological analysis of MTs explained this apparent discrepancy: while interphase MTs were depolymerized in cells expressing either Op18 derivative, apparently normal mitotic spindles mere formed only in cells overexpressing wild-type Op18, This result correlates with our finding that only mutated Op18 causes a block during mitosis. Hence, we conclude that Op18 decreases MT stability and that this activity of Op18 is subject to cell cycle regulation by CDKs.