Published online 9 January 2006. doi:10.1083/jcb1722iti2
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 172, Number 2, 164-164
Stat3 stabilizes microtubules
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Microtubules (top) get chewed up when Stat3 is missing (bottom).
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The STAT proteins are well-known as signaling proteins and transcription factors. But Ng et al. (page 245) report that Stat3 also functions in the cytoplasm, stabilizing microtubules by directly binding to and inhibiting the activity of a microtubule-destabilizing protein.
Stat3 functions in a variety of processes, including proliferation, survival, tumorigenesis, and migration. In each case, except migration, the protein works via transcriptional control of downstream effector proteins. How the protein controls migration is uncertain, though it is clear that cells lacking Stat3 do not migrate efficiently in vivo or in vitro.
Ng et al. found that Stat3 binds to stathmin, a protein that accelerates depolymerization of microtubules by binding to tubulin subunits. Stat3 bound stathmin via stathmin's tubulin-binding domain, blocking its depolymerizing activity.
Cultured cells lacking Stat3 showed a disordered microtubule network. However, expression of a transcriptionally inactive form of Stat3 rescued the phenotype, suggesting that nuclear signaling by Stat3 was not required. Moreover, down-regulation of stathmin partially rescued the Stat3 migration phenotype, but did not affect phosphorylation or transcriptional activity of Stat3 in normal cells.
The team is now looking to find out exactly how Stat3 affects microtubule dynamics. Because stathmin down-regulation only partially rescues the Stat3-null phenotype, Ng et al. hypothesize that Stat3 has another, as yet undiscovered, role in migration. Regardless of what comes next, the work demonstrates that the Stat3 previously detected in the cytoplasm is not just waiting to enter the nucleus.
Rabiya S. Tuma
rabiya@nasw.org
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