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Published on: November 17, 2023
Stat3 regulates microtubules by antagonizing the depolymerization activity of stathmin
Dominic Chi Hiung Ng1, Bao Hong Lin, Cheh Peng Lim
1Signal Transduction Laboratory, Institute of Molecular and Cell Biology, Singapore 138673, Republic of Singapore.
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.
Insights
Signal transducer and activator of transcription 3 (Stat3) interacts with stathmin, a microtubule-destabilizing protein. This interaction stabilizes microtubules and promotes cell migration, revealing a novel non-transcriptional role for Stat3.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Signal transducer and activator of transcription 3 (Stat3) is crucial for cytokine signaling and various biological processes.
- Stat3's function was previously thought to be solely transcriptional, occurring in the nucleus.
Purpose of the Study:
- To investigate a potential interaction between Stat3 and the microtubule-destabilizing protein stathmin.
- To elucidate the role of Stat3 in microtubule dynamics and cell migration beyond its transcriptional activity.
Main Methods:
- Investigated the interaction between Stat3 and stathmin.
- Assessed the effect of Stat3 on microtubule stabilization and cell migration.
- Examined stathmin's effect on Stat3-deficient cells.
- Performed in vitro tubulin polymerization assays with recombinant Stat3.
Main Results:
- Stat3 interacts with stathmin, a microtubule-destabilizing protein.
- Stat3 expression is necessary for microtubule stabilization and cell migration.
- Stat3 expression confers resistance to stathmin-induced microtubule destabilization.
- Stat3 antagonizes stathmin's inhibitory effect on tubulin polymerization in vitro.
Conclusions:
- Stat3 modulates the microtubule network by binding to stathmin.
- Stat3 antagonizes stathmin's microtubule destabilization activity, revealing a novel non-transcriptional function.
- This interaction is critical for maintaining microtubule stability and facilitating cell migration.
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