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.
Marklund
U
U
Department of Cell and Molecular Biology, University of Umeå, Sweden.
Larsson
N
N
Gradin
H M
HM
Brattsand
G
G
Gullberg
M
M
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