Stat3 regulates microtubules by antagonizing the depolymerization activity of stathmin.
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.
Ng
Dominic Chi Hiung
DC
Signal Transduction Laboratory, Institute of Molecular and Cell Biology, Singapore 138673, Republic of Singapore.
Lin
Bao Hong
BH
Lim
Cheh Peng
CP
Huang
Guochang
G
Zhang
Tong
T
Poli
Valeria
V
Cao
Xinmin
X
D000818:Animals; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D006801:Humans; D051379:Mice; D008870:Microtubules / Q000378:metabolism*; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D050777:Stathmin / Q000235:genetics / Q000378:metabolism*; D014404:Tubulin / Q000235:genetics / Q000378:metabolism; D020798:Two-Hybrid System Techniques
D009414:Nerve Growth Factors; D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins; D050796:STAT3 Transcription Factor; C112285:STMN3 protein, human; D050777:Stathmin; D014404:Tubulin