NRIP1
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Nuclear receptor-interacting protein 1 repression 1 | |||||||||
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Identifiers | |||||||||
Symbol | NRIP1_repr_1 | ||||||||
Pfam | PF15687 | ||||||||
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Nuclear receptor-interacting protein 1 repression 2 | |||||||||
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Identifiers | |||||||||
Symbol | NRIP1_repr_2 | ||||||||
Pfam | PF15688 | ||||||||
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Nuclear receptor-interacting protein 1 repression 3 | |||||||||
---|---|---|---|---|---|---|---|---|---|
Identifiers | |||||||||
Symbol | NRIP1_repr_3 | ||||||||
Pfam | PF15689 | ||||||||
|
Nuclear receptor-interacting protein 1 repression 4 | |||||||||
---|---|---|---|---|---|---|---|---|---|
Identifiers | |||||||||
Symbol | NRIP1_repr_4 | ||||||||
Pfam | PF15690 | ||||||||
|
Nuclear receptor-interacting protein 1 (NRIP1) also known as receptor-interacting protein 140 (RIP140) is a protein that in humans is encoded by the NRIP1 gene.[1][2]
Contents
Function
Nuclear receptor interacting protein 1 (NRIP1) is a nuclear protein that specifically interacts with the hormone-dependent activation domain AF2 of nuclear receptors. Also known as RIP140, this protein is a key regulator which modulates transcriptional activity of a variety of transcription factors, including the estrogen receptor.[3]
RIP140 has an important role in regulating lipid and glucose metabolism,[4] and regulates gene expression in metabolic tissues including heart,[5] skeletal muscle,[6] and liver.[7] A major role for RIP140 in adipose tissue is to block the expression of genes involved in energy dissipation and mitochondrial uncoupling, including uncoupling protein 1 and carnitine palmitoyltransferase 1b.[8]
Estrogen-related receptor alpha (ERRa) can activate RIP140 during adipogenesis, by means of directly binding to an estrogen receptor element/ERR element and indirectly through Sp1 binding to the proximal promoter.[9]
RIP140 suppresses the expression of mitochondrial proteins succinate dehydrogenase complex b and CoxVb and acts as a negative regulator of glucose uptake in mice.[10]
Knockout studies
Knockout mice that completely lack the RIP140 molecule are lean and stay lean, even on a rich diet.[11]
Knockout mice (females) are also infertile because they fail to ovulate.[12] Failure of ovulation in these mice is caused by lack of cumulus expansion and altered expression of various genes, including amphiregulin, in ovarian follicles.[13][14]
Clinical significance
RIP140 is part of the chain by which tumors can cause cachexia.[15][16]
Levels of RIP140 expression in various tissues varies during aging in mice, suggesting changes in metabolic function.[17] RIP140 is implicated in certain human disease processes. In morbid obesity, RIP140 levels are down-regulated in visceral adipose tissue.[18] In breast cancer, RIP140 is involved in regulation of E2F1, an oncogene which discriminates between luminal and basal types of tumours. RIP140 has an influence upon cancer phenotype and prognosis.[19] In addition, RIP140 has a role in inflammation, since it acts as a coactivator for NFkappaB/RelA-dependent cytokine gene expression. Lack of RIP140 leads to an inhibition of proinflammatory pathways in macrophages.[20]
Interactions
NRIP1 has been shown to interact with:
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See also
References
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Further reading
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External links
- NRIP1 protein, human at the US National Library of Medicine Medical Subject Headings (MeSH)
- NURSA C258
This article incorporates text from the United States National Library of Medicine, which is in the public domain.