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MBC in Press, published online ahead of print April 23, 2008
Mol. Biol. Cell 10.1091/mbc.E08-01-0058

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Submitted on January 22, 2008
Revised on March 11, 2008
Accepted on April 11, 2008

Global Regulation of the Interphase Microtubule System by Abundantly Expressed Op18/Stathmin

Mikael E Sellin, Per Holmfeldt, Sonja Stenmark, and Martin Gullberg

Department of Molecular Biology, Umeå University, SE-901 87 Umeå, Sweden

Monitoring Editor: Yixian Zheng

Op18/stathmin (Op18), a conserved microtubule depolymerizing and tubulin heterodimer binding protein, is a major interphase regulator of tubulin monomer-polymer partitioning in diverse cell types in which Op18 is abundant. Here we addressed the question of whether the microtubule regulatory function of Op18 includes regulation of tubulin heterodimer synthesis. We used two human cell model systems, K562 and Jurkat, combined with strategies for regulatable overexpression or depletion of Op18. Although Op18 depletion caused extensive overpolymerization and increased microtubule content in both cell types, we did not detect any alteration in polymer stability. Interestingly, however, we found that Op18 mediates positive regulation of tubulin heterodimer content in Jurkat cells, which was not observed in K562 cells. By analysis of cells treated with microtubule-poisoning drugs, we found that Jurkat cells regulate tubulin mRNA levels by a posttranscriptional mechanism similarly to normal primary cells, while this mechanism is nonfunctional in K562 cells. We present evidence that Op18 mediates posttranscriptional regulation of tubulin mRNA in Jurkat cells through the same basic autoregulatory mechanism as microtubule-poisoning drugs. This, combined with potent regulation of tubulin monomer-polymer partitioning, enables Op18 to exert global regulation of the microtubule system.


Address correspondence to: Martin Gullberg (martin.gullberg{at}molbiol.umu.se)







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