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Op18/Stathmin counteracts the activity of overexpressed tubulin-disrupting proteins in a human leukemia cell line
Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). (Gullberg)
Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). (Gullberg)
Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). (Gullberg)
Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). (Gullberg)
2008 (English)In: Experimental Cell Research, ISSN 0014-4827, E-ISSN 1090-2422, Vol. 314, no 6, 1367-77 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
New York: Academic Press , 2008. Vol. 314, no 6, 1367-77 p.
National Category
Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:umu:diva-20782DOI: 10.1016/j.yexcr.2007.12.018PubMedID: 18262179OAI: oai:DiVA.org:umu-20782DiVA: diva2:209537
Available from: 2009-03-25 Created: 2009-03-25 Last updated: 2011-10-21Bibliographically approved
In thesis
1. Cytoskeletal filament systems: assembly, regulation, and interplay in mammalian cells
Open this publication in new window or tab >>Cytoskeletal filament systems: assembly, regulation, and interplay in mammalian cells
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The cell represents the basic unit of structure and function for all life. The interior of a eukaryotic cell is organized by an extensive array of protein filaments – collectively referred to as the cytoskeleton. These filaments serve diverse essential functions, e.g. to provide mechanical resilience, facilitate intracellular transport, and enable cell polarization, locomotion and division. Here I have explored the mechanisms that regulate synthesis and assembly of two cytoskeletal filament systems – microtubules and septins – and how these interact in human cells. The present thesis is based on three principal discoveries. Firstly, we have found that the microtubule-destabilizing protein Op18/Stathmin also regulates synthesis of tubulin heterodimers, which are the building blocks for microtubules. Secondly, we have unraveled the general rules that govern assembly of mammalian septins into native polymerization-competent heterooligomers. Finally, our combined results point to a non-reciprocal interplay whereby interphase microtubules support a disc-like arrangement of septin filaments, which delineate static plasma membrane regions. I here discuss the physiological significance and implications of these findings.

Place, publisher, year, edition, pages
Umeå: Umeå universitet, Institutionen för molekylärbiologi, 2011. 68 p.
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1450
National Category
Cell and Molecular Biology
Research subject
cellforskning
Identifiers
urn:nbn:se:umu:diva-48508 (URN)978-91-7459-301-3 (ISBN)
Public defence
2011-11-11, Major Groove, Institutionen för Molekylärbiologi, Försörjningsvägen, Byggnad 6L, Umeå Universitet, Umeå, 09:00 (English)
Opponent
Supervisors
Available from: 2011-10-21 Created: 2011-10-20 Last updated: 2011-10-21Bibliographically approved

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Stenmark, SonjaGullberg, Martin

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