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Serum response factor is modulated by the SUMO-1 conjugation system
Kazuhito Matsuzaki1, Takeshi Minami, Masahide Tojo
1Department of Regeneration Medicine, Institute of Molecular Embryology and Genetics, Kumamoto University, 2-2-1 Honjo, 860-0811, Kumamoto, Japan.
Biochemical and Biophysical Research Communications
|June 6, 2003
Summary
Serum response factor (SRF) is modified by SUMO-1, impacting gene transcription. This sumoylation suppresses activated SRF, revealing a role for the SUMO-1 system in cellular serum response pathways.
Area of Science:
- Molecular Biology
- Cellular Signaling
Background:
- Serum response factor (SRF) regulates immediate-early gene transcription via signal transduction pathways.
- Promyelocytic leukemia protein (PML) interacts with SRF in transcriptional regulation.
- PML is known to associate with SUMO-1 modified proteins.
Purpose of the Study:
- To investigate the role of SUMO-1 modification on SRF.
- To determine the functional consequence of SRF sumoylation on gene transcription.
Main Methods:
- Site-directed mutagenesis to substitute lysine(147) of SRF with alanine.
- Analysis of SRF translocation to PML-nuclear bodies.
- Assessment of transcriptional activity under different cellular conditions (serum-starved vs. Rho A-stimulated).
Main Results:
- SRF is sumoylated by SUMO-1 at lysine(147) within its DNA-binding domain.
- SRF sumoylation does not affect its translocation to PML-nuclear bodies.
- A mutant SRF lacking sumoylation at K147 showed augmented transcriptional activity under Rho A stimulation, but not when serum-starved, indicating suppression of activated SRF by sumoylation.
Conclusions:
- SRF is a novel substrate for SUMO-1 modification.
- SUMO-1 conjugation to SRF acts as a negative regulator of its transcriptional activity, particularly under stimulated conditions.
- These findings highlight the importance of the SUMO-1 conjugating system in regulating cellular serum response.