Oncoprotein 18 is a phosphorylation-responsive regulator of microtubule dynamics

EMBO J. 1996 Oct 1;15(19):5290-8.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Cadmium / pharmacology
  • Cell Cycle / physiology*
  • Cyclin-Dependent Kinases / metabolism
  • DNA, Neoplasm / analysis
  • Edetic Acid / pharmacology
  • Gene Expression Regulation / drug effects
  • Humans
  • Leukemia, Erythroblastic, Acute
  • Metaphase
  • Microtubule Proteins*
  • Microtubules / drug effects
  • Microtubules / metabolism*
  • Mutation
  • Nocodazole / pharmacology
  • Paclitaxel / pharmacology
  • Phenotype
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism
  • Phosphoproteins / physiology*
  • Phosphorylation
  • Polymers / analysis
  • Stathmin
  • Tubulin / analysis
  • Tumor Cells, Cultured

Substances

  • DNA, Neoplasm
  • Microtubule Proteins
  • Phosphoproteins
  • Polymers
  • STMN1 protein, human
  • Stathmin
  • Tubulin
  • Cadmium
  • Edetic Acid
  • Cyclin-Dependent Kinases
  • Paclitaxel
  • Nocodazole