Nuclear receptor-interacting protein 1 (NRIP1) also known as receptor-interacting protein 140 (RIP140) is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

that in humans is encoded by the ''NRIP1''

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

Function

Nuclear receptor interacting protein 1 (NRIP1) is a nuclear protein that specifically interacts with the hormone-dependent activation domain AF2 of

nuclear receptor In the field of molecular biology, nuclear receptors are a class of proteins responsible for sensing steroids, thyroid hormones, vitamins, and certain other molecules. These receptors work with other proteins to regulate the expression of speci ...

s. Also known as RIP140, this protein is a key regulator which modulates transcriptional activity of a variety of transcription factors, including the

estrogen receptor Estrogen receptors (ERs) are a group of proteins found inside cells. They are receptors that are activated by the hormone estrogen ( 17β-estradiol). Two classes of ER exist: nuclear estrogen receptors (ERα and ERβ), which are members of the ...

. RIP140 has an important role in regulating lipid and glucose metabolism, and regulates gene expression in metabolic tissues including heart, skeletal muscle, and liver. A major role for RIP140 in adipose tissue is to block the expression of genes involved in energy dissipation and

mitochondrial A mitochondrion (; ) is an organelle found in the cells of most Eukaryotes, such as animals, plants and fungi. Mitochondria have a double membrane structure and use aerobic respiration to generate adenosine triphosphate (ATP), which is use ...

uncoupling, including

uncoupling protein 1 Thermogenin (called uncoupling protein by its discoverers and now known as uncoupling protein 1, or UCP1) is a mitochondrial carrier protein found in brown adipose tissue (BAT). It is used to generate heat by non-shivering thermogenesis, and makes ...

and carnitine palmitoyltransferase 1b.

Estrogen-related receptor alpha Estrogen-related receptor alpha (ERRα), also known as NR3B1 (nuclear receptor subfamily 3, group B, member 1), is a nuclear receptor that in humans is encoded by the ''ESRRA'' (Estrogen Related Receptor Alpha) gene. ERRα was originally cloned b ...

(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. RIP140 suppresses the expression of mitochondrial proteins

succinate dehydrogenase Succinate dehydrogenase (SDH) or succinate-coenzyme Q reductase (SQR) or respiratory complex II is an enzyme complex, found in many bacterial cells and in the inner mitochondrial membrane of eukaryotes. It is the only enzyme that participates i ...

complex b and CoxVb and acts as a negative regulator of glucose uptake in mice.

Knockout studies

Knockout mice A knockout mouse, or knock-out mouse, is a genetically modified mouse (''Mus musculus'') in which researchers have inactivated, or "knocked out", an existing gene by replacing it or disrupting it with an artificial piece of DNA. They are importan ...

that completely lack the RIP140 molecule are lean and stay lean, even on a rich diet. Knockout mice (females) are also infertile because they fail to

ovulate Ovulation is the release of eggs from the ovaries. In women, this event occurs when the ovarian follicles rupture and release the secondary oocyte ovarian cells. After ovulation, during the luteal phase, the egg will be available to be fertilized ...

. Failure of ovulation in these mice is caused by lack of

cumulus Cumulus clouds are clouds which have flat bases and are often described as "puffy", "cotton-like" or "fluffy" in appearance. Their name derives from the Latin ''cumulo-'', meaning ''heap'' or ''pile''. Cumulus clouds are low-level clouds, gener ...

expansion and altered expression of various genes, including

amphiregulin Amphiregulin, also known as AREG, is a protein synthesized as a transmembrane glycoprotein with 252 aminoacids and it is encoded by the ''AREG'' gene. in humans. Function The protein encoded by this gene is a member of the epidermal growth fac ...

, in

ovarian follicles An ovarian follicle is a roughly spheroid cellular aggregation set found in the ovaries. It secretes hormones that influence stages of the menstrual cycle. At the time of puberty, women have approximately 200,000 to 300,000 follicles, each with t ...

Clinical significance

RIP140 is part of the chain by which tumors can cause

cachexia Cachexia () is a complex syndrome associated with an underlying illness, causing ongoing muscle loss that is not entirely reversed with nutritional supplementation. A range of diseases can cause cachexia, most commonly cancer, congestive heart f ...

. Levels of RIP140 expression in various tissues varies during aging in mice, suggesting changes in metabolic function. RIP140 is implicated in certain human disease processes. In morbid obesity, RIP140 levels are down-regulated in visceral adipose tissue. 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. In addition, RIP140 has a role in inflammation, since it acts as a coactivator for NFkappaB/

RelA Transcription factor p65 also known as nuclear factor NF-kappa-B p65 subunit is a protein that in humans is encoded by the ''RELA'' gene. RELA, also known as p65, is a REL-associated protein involved in NF-κB heterodimer formation, nuclear tran ...

-dependent

cytokine Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in autocrin ...

gene expression. Lack of RIP140 leads to an inhibition of proinflammatory pathways in

macrophage Macrophages (abbreviated as M φ, MΦ or MP) ( el, large eaters, from Greek ''μακρός'' (') = large, ''φαγεῖν'' (') = to eat) are a type of white blood cell of the immune system that engulfs and digests pathogens, such as cancer cel ...

Interactions

NRIP1 has been shown to

interact Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization using innovative strategies to advocate for the legal and human rights of children with intersex traits. The organizati ...

with: *

AHR Ahr () is a river in Germany, a left tributary of the Rhine. Its source is at an elevation of approximately above sea level in Blankenheim in the Eifel, in the cellar of a timber-frame house near the castle of Blankenheim. After it crosses fro ...

, *

CTBP1 C-terminal-binding protein 1 also known as CtBP1 is a protein that in humans is encoded by the ''CTBP1'' gene. CtBP1 is one of two CtBP proteins, the other protein being CtBP2. Function The CtBP1 protein was originally identified as a human prote ...

CTBP2 C-terminal-binding protein 2 also known as CtBP2 is a protein that in humans is encoded by the ''CTBP2'' gene. Function The CtBPs - CtBP1 and CtBP2 in mammals - are among the best characterized transcriptional corepressors. They typically turn ...

, *

DAX1 DAX1 (dosage-sensitive sex reversal, adrenal hypoplasia critical region, on chromosome X, gene 1) is a nuclear receptor protein that in humans is encoded by the ''NR0B1'' gene (nuclear receptor subfamily 0, group B, member 1). The ''NR0B1'' gene i ...

, *

HDAC5 Histone deacetylase 5 is an enzyme that in humans is encoded by the ''HDAC5'' gene. Function Histones play a critical role in transcriptional regulation, cell cycle progression, and developmental events. Histone acetylation/deacetylation alte ...

, * NR1B1, * NR2B1, *

NR3A1 Estrogen receptor alpha (ERα), also known as NR3A1 (nuclear receptor subfamily 3, group A, member 1), is one of two main types of estrogen receptor, a nuclear receptor (mainly found as a chromatin-binding protein) that is activated by the sex ...

, * NR3C1, * NR5A1, and *

YWHAQ 14-3-3 protein theta is a protein that in humans is encoded by the ''YWHAQ'' gene. Function This gene product belongs to the 14-3-3 family of proteins that mediate signal transduction by binding to phosphoserine-containing proteins. This highl ...

References

External links

* *
PDBe-KB
provides an overview of all the structure information available in the PDB for Human Nuclear receptor-interacting protein 1 (NRIP1) {{Transcription coregulators Gene expression Transcription coregulators