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Functional analysis of the nuclear receptor co repressor RIP140

Reference	BB/C504327/1
Principal Investigator / Supervisor	Professor Malcolm Parker
Co-Investigators / Co-Supervisors	Professor Stephen Dilworth, Dr Roger White
Institution	Imperial College London
Department	Dept of Medicine
Funding type	Research
Value (£)	800,129
Status	Completed
Type	Research Grant
Start date	10/01/2005
End date	09/06/2010
Duration	65 months

Abstract

Steroid hormones, certain vitamins and dietary fatty acids regulate a vast array of physiological responses in vertebrates by regulating the activity of specific genes. They bind to specific nuclear receptors that function as ligand dependent transcription factors. Their action is mediated by coactivators or corepessors many of which remodel chromatin and either stimulate or inhibit transcription from target genes. We are focusing on the function of a corepressor we identified called RIP140. It is essential for fertility and energy homeostasis. Mice without the RIP140 gene fail to ovulate and accumulate very little fat. The lean phenotype seems to result from an increase in the expression of genes involved in energy expenditure. Thus RIP140 appears to play a crucial role in preventing the expression of certain genes in particular tissues that would otherwise disrupt their function. We have found that RIP140 contains four distinct regions that repress transcription but little is known about their mechanism of action. We propose to identify proteins which bind to each region by proteomic approaches and then characterise their function as enzymes or bridging proteins. We intend to investigate their mechanism of action in adipocyte cell cultures and in adipose tissue from transgenic mice. Finally we will determine whether the RIP140 protein complexes are modified when they function in fat and in the ovary during the oestrous cycle to provide insight into signalling pathways that regulate their assembly.

Summary

unavailable

Committee	Closed Committee - Animal Sciences (AS)
Research Topics	X – not assigned to a current Research Topic
Research Priority	X – Research Priority information not available
Research Initiative	Proteomics and Cell Function (PCF) [2003-2004]
Funding Scheme	X – not Funded via a specific Funding Scheme

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