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 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.
Department of Cell and Molecular Biology, University of Umeå, Sweden.
U
U
Marklund
N
N
Larsson
H M
HM
Gradin
G
G
Brattsand
M
M
Gullberg
D000595:Amino Acid Sequence; D002104:Cadmium / Q000494:pharmacology; D002453:Cell Cycle / Q000502:physiology*; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D004273:DNA, Neoplasm / Q000032:analysis; D004492:Edetic Acid / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D004915:Leukemia, Erythroblastic, Acute; D008677:Metaphase; D008868:Microtubule Proteins; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism*; D009154:Mutation; D015739:Nocodazole / Q000494:pharmacology; D017239:Paclitaxel / Q000494:pharmacology; D010641:Phenotype; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D010766:Phosphorylation; D011108:Polymers / Q000032:analysis; D050777:Stathmin; D014404:Tubulin / Q000032:analysis; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D008868:Microtubule Proteins; D010750:Phosphoproteins; D011108:Polymers; C493995:STMN1 protein, human; D050777:Stathmin; D014404:Tubulin; D002104:Cadmium; D004492:Edetic Acid; D018844:Cyclin-Dependent Kinases; D017239:Paclitaxel; D015739:Nocodazole