Marklund U, Larsson N, Gradin H M, Brattsand G, Gullberg M
Department of Cell and Molecular Biology, University of Umeå, Sweden.
EMBO J. 1996 Oct 1;15(19):5290-8.
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 were 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.
癌蛋白18（Op18，也称为p19、p18、prosolin或stathmin）是一种功能未知的胞质蛋白。Op18的磷酸化受细胞周期蛋白依赖性激酶（CDK）调控，“缺乏CDK靶位点突变体”的表达导致一种表型，表明Op18在有丝分裂过程中发挥作用。这种表型与Op18是微管（MT）动力学的磷酸化反应调节因子这一观点相符。因此，在本研究中，我们分析了诱导表达野生型或突变型Op18的细胞中的微管。结果表明，野生型Op18和一个CDK靶位点突变体均能有效引发微管的快速解聚。这一结果与它们在细胞周期表型上的明显差异形成对比。对微管的形态学分析解释了这一明显的差异：虽然在表达任何一种Op18衍生物的细胞中，间期微管都会解聚，但只有在过表达野生型Op18的细胞中才能形成明显正常的有丝分裂纺锤体。这一结果与我们的发现相关，即只有突变型Op18会在有丝分裂过程中导致阻滞。因此，我们得出结论，Op18会降低微管稳定性，且Op18的这一活性受CDK的细胞周期调控。
