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J. Cell Biol. 172 (2): 245-257

Copyright © 2006 by the Rockefeller University Press.

Article

Stat3 regulates microtubules by antagonizing the depolymerization activity of stathmin

Dominic Chi Hiung Ng1, Bao Hong Lin1, Cheh Peng Lim1, Guochang Huang1, Tong Zhang1, Valeria Poli2, , and Xinmin Cao1

1 Signal Transduction Laboratory, Institute of Molecular and Cell Biology, Singapore 138673, Republic of Singapore
2 Department of Genetics, Biology, and Biochemistry, University of Turin, 10126 Turin, Italy

Correspondence to Xinmin Cao: mcbcaoxm{at}imcb.a-star.edu.sg

Abstract: Stat3 is a member of the signal transducer and activator of transcription family, which is important in cytokine signaling. Gene ablation studies have revealed a requirement for Stat3 in diverse biological processes (Akira, S. 2000. Oncogene. 19: 2607–2611; Levy, D.E., and C.K. Lee. 2002. J. Clin. Invest. 109:1143–1148). Previously, the function of Stat3 had been attributed exclusively to its transcriptional activity in the nucleus. In this study, we reveal an interaction between Stat3 and the microtubule (MT)-destabilizing protein stathmin. Stathmin did not overtly affect ligand-stimulated Stat3 activation. In contrast, the expression of Stat3 is required for the stabilization of MTs and cell migration. We further demonstrate that Stat3-containing cells are resistant to the MT-destabilizing effect of stathmin overexpression. In addition, down-regulation of stathmin protein levels in Stat3-deficient cells partially reversed the MT and migration deficiencies. Recombinant Stat3 was also capable of reversing stathmin inhibition of tubulin polymerization in vitro. Our results indicate that Stat3 modulates the MT network by binding to the COOH-terminal tubulin-interacting domain of stathmin and antagonizing its MT destabilization activity.

T. Zhang's present address is Department of Medicine, University of California, San Diego, La Jolla, CA 92093.

Abbreviations used in this paper: {Delta}St3, Stat3 deficient; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; HU, hydroxyurea; IL-6, interleukin 6; MEF, murine embryonic fibroblast; MT, microtubule; SCG10, super cervical ganglion protein 10; SCLIP, SCG10-like protein; siRNA, short inhibitory RNA; SLD, stathmin-like domain; TCL, total cell lysate; WT, wild type.

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