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PIAS1 interacts with and represses SOX9 transactivation activity
Hyun Ju Oh1, Tatsuo Kido, Yun-Fai Chris Lau
1Department of Medicine, VA Medical Center, University of California, San Francisco, California, USA.
Molecular Reproduction and Development
|April 19, 2007
Summary
The protein PIAS1 regulates the transcription factor SOX9 activity by enhancing its SUMOylation. This interaction impacts SOX9
Area of Science:
- Molecular Biology
- Developmental Biology
- Epigenetics
Background:
- SOX9 is a crucial transcription factor involved in development, but its regulatory mechanisms are not fully understood.
- Post-translational modifications like SUMOylation are key to regulating protein function.
Purpose of the Study:
- To identify regulators of SOX9 activity.
- To investigate the role of PIAS1 in SOX9 regulation.
- To elucidate the mechanism by which PIAS1 affects SOX9 function, including SUMOylation.
Main Methods:
- GST pull-down, co-immunoprecipitation, and co-localization assays to confirm SOX9-PIAS1 interaction.
- Reporter assays to assess SOX9 transcriptional activity.
- Site-directed mutagenesis to study the role of SOX9 lysine 396 in SUMOylation and activity.
Main Results:
- SOX9 directly interacts with PIAS1 in vitro and in vivo.
- PIAS1 enhances SUMOylation of SOX9 at lysine 396, affecting its transcriptional activity.
- PIAS1 represses SOX9 activity through SUMOylation-dependent and independent mechanisms.
Conclusions:
- PIAS1 is a novel regulator of SOX9 transcriptional activity.
- PIAS1-mediated SUMOylation of SOX9 plays a significant role in modulating its function.
- PIAS1 represses SOX9 via at least two SUMO-ligase dependent pathways.
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