SUMOylation modulates the transcription repressor function of RIP140
Miia M Rytinki1, Jorma J Palvimo
1Institute of Biomedicine/Medical Biochemistry, University of Kuopio, FI-70211 Kuopio, Finland.
The Journal of Biological Chemistry
|January 24, 2008
Summary
Receptor-interacting protein 140 (RIP140) repression is modulated by SUMOylation. SUMOylation of RIP140
Area of Science:
- Molecular Biology
- Epigenetics
- Nuclear Receptor Signaling
Background:
- Receptor-interacting protein 140 (RIP140) is a corepressor regulating energy metabolism and fertility.
- RIP140 possesses four repression domains (RD1-RD4), with mechanisms for RD3 and RD4 repression being unclear.
- Small ubiquitin-like modifier (SUMO) conjugation is linked to transcriptional repression.
Purpose of the Study:
- To investigate the role of SUMOylation in RIP140's repressive activity.
- To identify SUMOylation sites within RIP140 and their functional consequences.
Main Methods:
- Site-directed mutagenesis to alter RIP140 SUMOylation sites.
- Analysis of RIP140's transcriptional repressor function.
- Assessment of RIP140 subnuclear localization.
Main Results:
- Two lysines (Lys756 in RD3, Lys1154 in RD4) are SUMOylated by SUMO-1 and SUMO-2.
- Mutating these SUMOylation sites impaired RIP140's repressor function and estrogen receptor alpha repression.
- SUMO-1 conjugation affected RIP140's subnuclear distribution.
Conclusions:
- SUMOylation of RIP140 at RD3 and RD4 is a novel regulatory mechanism.
- This modification impacts RIP140's function in transcriptional control.
- Findings suggest implications for RIP140's role in gene network regulation.
