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Describing a Transcription Factor Dependent Regulation of the MicroRNA Transcriptome
Published on: June 15, 2016
STAT3 association with microtubules and its activation are independent of HDAC6 activity
Bing Yan1, Songbo Xie, Zhu Liu
11 State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University , Tianjin, China .
Abstract:
Signal transducer and activator of transcription 3 (STAT3) is an important oncogenic transcription factor residing in the cytoplasm in the resting cells. Upon stimulation, STAT3 is activated and translocated to the nucleus to regulate target genes. Although the canonical transcriptional function of STAT3 has been intensively studied, less is known about its cytoplasmic localization. In this study, by immunoprecipitation, microtubule cosedimentation, and immunofluorescence assays, we present the first evidence that cytoplasmic STAT3 interacts with both tubulin and microtubules. By using small-molecule inhibitor approaches, we further demonstrate that the localization of STAT3 on microtubules and its activation are independent of histone deacetylase 6 (HDAC6) activity. In addition, disruption of microtubule dynamics does not alter the activation and nuclear translocation of STAT3 in response to interleukin-6 treatment. These findings reveal that cytoplasmic STAT3 is physically associated with microtubules, whereas its activation and nuclear translocation are independent of microtubule dynamics, implicating that the association of STAT3 with microtubules might be involved in the regulation of noncanonical functions of STAT3 in the cytoplasm.
Insights
Signal transducer and activator of transcription 3 (STAT3) interacts with microtubules in the cytoplasm. This association is independent of microtubule dynamics and HDAC6 activity, suggesting roles in noncanonical cellular functions.
Area of Science:
- Cell Biology
- Molecular Biology
- Cancer Research
Background:
- Signal transducer and activator of transcription 3 (STAT3) is a key oncogenic factor.
- STAT3's canonical nuclear role is well-studied, but its cytoplasmic functions are less understood.
- Cytoplasmic localization of STAT3 is critical for its noncanonical functions.
Purpose of the Study:
- To investigate the interaction of cytoplasmic STAT3 with cellular components.
- To determine the role of microtubules and HDAC6 in STAT3 localization and activation.
- To elucidate the noncanonical functions of STAT3 in the cytoplasm.
Main Methods:
- Immunoprecipitation assays to identify interacting proteins.
- Microtubule cosedimentation assays to assess binding.
- Immunofluorescence microscopy for cellular localization.
- Small-molecule inhibitors to probe functional dependencies.
Main Results:
- Cytoplasmic STAT3 directly interacts with tubulin and microtubules.
- STAT3 localization on microtubules and its activation are independent of HDAC6.
- Disruption of microtubule dynamics does not affect STAT3 activation or nuclear translocation.
- Evidence suggests STAT3 association with microtubules regulates cytoplasmic functions.
Conclusions:
- Cytoplasmic STAT3 physically associates with microtubules.
- STAT3 activation and nuclear translocation are independent of microtubule dynamics.
- Microtubule-STAT3 interaction may mediate STAT3's noncanonical cytoplasmic roles.
- Findings open new avenues for exploring STAT3 in cancer and other cellular processes.
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