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.[5][6]
| Nuclear receptor-interacting protein 1 repression 1 | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Identifiers | |||||||||
| Symbol | NRIP1_repr_1 | ||||||||
| Pfam | PF15687 | ||||||||
| |||||||||
| Nuclear receptor-interacting protein 1 repression 2 | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Identifiers | |||||||||
| Symbol | NRIP1_repr_2 | ||||||||
| Pfam | PF15688 | ||||||||
| |||||||||
| 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 | ||||||||
| |||||||||
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.[7]
RIP140 has an important role in regulating lipid and glucose metabolism,[8] and regulates gene expression in metabolic tissues including heart,[9] skeletal muscle,[10] and liver.[11] 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.[12]
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.[13]
RIP140 suppresses the expression of mitochondrial proteins succinate dehydrogenase complex b and CoxVb and acts as a negative regulator of glucose uptake in mice.[14]
Knockout studies
Knockout mice that completely lack the RIP140 molecule are lean and stay lean, even on a rich diet.[15]
Knockout mice (females) are also infertile because they fail to ovulate.[16] Failure of ovulation in these mice is caused by lack of cumulus expansion and altered expression of various genes, including amphiregulin, in ovarian follicles.[17][18]
Clinical significance
RIP140 is part of the chain by which tumors can cause cachexia.[19][20]
Levels of RIP140 expression in various tissues varies during aging in mice, suggesting changes in metabolic function.[21] RIP140 is implicated in certain human disease processes. In morbid obesity, RIP140 levels are down-regulated in visceral adipose tissue.[22] 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.[23] 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.[24]
Interactions
NRIP1 has been shown to interact with:
See also
References
Further reading
External links
- NRIP1 protein, human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- NURSA C258
- PDBe-KB provides an overview of all the structure information available in the PDB for Human Nuclear receptor-interacting protein 1 (NRIP1)
This article incorporates text from the United States National Library of Medicine, which is in the public domain.