title: Op18/Stathmin counteracts the activity of overexpressed tubulin-disrupting proteins in a human leukemia cell line.
abstract: Op18/stathmin (Op18) is a phosphorylation-regulated and differentially expressed microtubule-destabilizing protein in animal cells. Op18 regulates tubulin monomer-polymer partitioning of the interphase microtubule system and forms complexes with tubulin heterodimers. Recent reports have shown that specific tubulin-folding cofactors and related proteins may disrupt tubulin heterodimers. We therefore investigated whether Op18 protects unpolymerized tubulin from such disruptive activities. Our approach was based on inducible overexpression of two tubulin-disrupting proteins, namely TBCE, which is required for tubulin biogenesis, and E-like, which has been proposed to regulate tubulin turnover and microtubule stability. Expression of either of these proteins was found to cause a rapid degradation of both alpha-tubulin and beta-tubulin subunits of unpolymerized, but not polymeric, tubulin heterodimers. We found that depletion of Op18 by means of RNA interference increased the susceptibility of tubulin to TBCE or E-like mediated disruption, while overexpressed Op18 exerted a tubulin-protective effect. Tubulin protection was shown to depend on Op18 levels, binding affinity, and the partitioning between tubulin monomers and polymers. Hence, the present study reveals that Op18 at physiologically relevant levels functions to preserve the integrity of tubulin heterodimers, which may serve to regulate tubulin turnover rates.
authors.affiliation: Department of Molecular Biology, Umeå University, Umeå, Sweden. Mikael.sellin@molbiol.umu.se
authors.forename: Mikael E
authors.initials: ME
authors.lastname: Sellin
authors.forename: Per
authors.initials: P
authors.lastname: Holmfeldt
authors.forename: Sonja
authors.initials: S
authors.lastname: Stenmark
authors.forename: Martin
authors.initials: M
authors.lastname: Gullberg
mesh_terms: D019281:Dimerization; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D020014:K562 Cells; D016547:Kinesins / Q000378:metabolism; D007938:Leukemia / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D008565:Membrane Proteins / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D018832:Molecular Chaperones / Q000378:metabolism*; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D050777:Stathmin / Q000235:genetics / Q000378:metabolism*; D014404:Tubulin / Q000378:metabolism
chemical_list: C091489:KIF2C protein, human; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D018832:Molecular Chaperones; C493995:STMN1 protein, human; C063314:STMN2 protein, human; D050777:Stathmin; C469270:TBCE protein, human; C503569:TBCEL protein, human; D014404:Tubulin; D016547:Kinesins