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Originally published as MBC in Press, 10.1091/mbc.E08-01-0058 on April 23, 2008

Vol. 19, Issue 7, 2897-2906, July 2008

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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

Submitted January 22, 2008; Revised March 11, 2008; Accepted April 11, 2008
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, whereas 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.


This was published online ahead of print in MBC in Press (http://www.molbiolcell.org/cgi/doi/10.1091/mbc.E08-01-0058) on April 23, 2008.

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

Abbreviations used: Op18, Op18/stathmin; shRNA, short hairpin RNA.







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