Affinage

NRIP1

Nuclear receptor-interacting protein 1 · UniProt P48552

Length
1158 aa
Mass
126.9 kDa
Annotated
2026-04-29
100 papers in source corpus 42 papers cited in narrative 42 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NRIP1 (RIP140) is a ligand-dependent transcriptional corepressor that serves as a master brake on energy expenditure, oxidative metabolism, and reproductive gene programs by bridging nuclear receptors to repressive chromatin-modifying machinery. It engages the AF2 domains of diverse nuclear receptors (ERα, GR, PPARs, RARs, TR, TR2, ERRα, SF-1) via multiple LXXLL motifs and recruits HDAC3, CtBP, G9a, and DNMT3b to silence target loci through histone deacetylation, histone methylation, and DNA methylation (PMID:11278635, PMID:17972916, PMID:19778926). Its corepressor potency is tuned by a sequential post-translational modification cascade — Erk2 phosphorylation promotes p300-mediated acetylation to enhance repression, while PKCε phosphorylation triggers 14-3-3 binding, PRMT1-catalyzed arginine methylation, and exportin-1-dependent nuclear export — and upon export, cytoplasmic RIP140 acquires non-genomic functions including inhibition of GLUT4 trafficking via AS160 and promotion of lipolysis via perilipin interaction on lipid droplets (PMID:18628823, PMID:19945409, PMID:21504789). Nrip1-null mice are lean, resistant to diet-induced obesity with derepressed UCP1 and mitochondrial gene programs in white adipose tissue and muscle, and female nulls are completely infertile due to anovulation, while cardiac-specific deletion protects against heart failure (PMID:15155905, PMID:11100122, PMID:36927960).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1995 High

    Identification of RIP140 as a ligand-dependent interactor of estrogen receptor AF2 established that nuclear receptors recruit cofactors beyond basal transcription factors, opening the question of whether RIP140 activates or represses transcription.

    Evidence In vitro binding, co-IP in intact cells, and reporter assays with estrogen receptor

    PMID:7641693

    Open questions at the time
    • Activation vs. repression function unresolved
    • Interaction with non-steroid receptors untested
  2. 1998 High

    Demonstration that RIP140 competes with the coactivator SRC-1 for receptor binding and suppresses PPAR/RXR-mediated transcription resolved its role as a competitive corepressor rather than a coactivator.

    Evidence Yeast two-hybrid, competition binding, and mammalian reporter assays with PPARα/γ and RXR

    PMID:8887632 PMID:9626662 PMID:9774688

    Open questions at the time
    • Mechanism of repression (enzymatic recruitment) not yet identified
    • In vivo relevance unestablished
  3. 2000 High

    Generation of Nrip1-null mice revealed an essential in vivo role: female infertility due to complete anovulation, proving RIP140 is non-redundant for ovarian function.

    Evidence Knockout mouse model with histological and endocrine phenotyping; ovarian transplantation confirmed ovary-intrinsic requirement

    PMID:11100122 PMID:11796527

    Open questions at the time
    • Target genes mediating anovulation unknown
    • Whether ovulatory defect reflects corepression of specific nuclear receptors unclear
  4. 2001 High

    Identification of CtBP and HDAC3 as recruited effectors, interacting through distinct motifs, established that RIP140 is not merely a passive competitor but actively scaffolds repressive enzyme complexes onto nuclear receptor targets.

    Evidence Co-IP, ChIP, mutagenesis of CtBP-binding PIDLSCK motif and C-terminal HDAC3-recruiting motif, with reporter validation

    PMID:11278635 PMID:11509661

    Open questions at the time
    • Whether CtBP and HDAC3 act on same or different target gene sets unknown
    • Additional repressive effectors not surveyed
  5. 2004 High

    The discovery that Nrip1-null mice are lean and obesity-resistant with derepressed UCP1 and mitochondrial uncoupling genes in white fat established RIP140 as a central gatekeeper of energy expenditure and adipocyte metabolic identity.

    Evidence Knockout mouse metabolic phenotyping, gene expression profiling, high-fat diet challenge

    PMID:15155905 PMID:16374519

    Open questions at the time
    • Which nuclear receptors mediate metabolic repression in adipose tissue not fully defined
    • Cell-autonomous vs. systemic contributions not separated
  6. 2005 High

    Mapping MAPK phosphorylation at Thr202/Thr207 showed that signaling pathways actively enhance RIP140 repressor potency by promoting HDAC recruitment, establishing post-translational regulation as a key control layer.

    Evidence Mass spectrometry, phospho-mimetic and phospho-dead mutagenesis, HDAC recruitment and reporter assays

    PMID:16093479

    Open questions at the time
    • Upstream signals activating this MAPK cascade in physiological context not identified
    • Whether phosphorylation affects all or specific target gene sets unknown
  7. 2007 High

    Discovery that RIP140 scaffolds both DNA methyltransferases and histone methyltransferases onto the Ucp1 enhancer expanded its mechanism from histone deacetylation to full epigenetic silencing including DNA methylation.

    Evidence ChIP and bisulfite genomic sequencing on Ucp1 enhancer in white adipocytes

    PMID:17972916

    Open questions at the time
    • Whether epigenetic scaffolding generalizes beyond Ucp1 to other metabolic genes untested
    • Identity of recruited DNA methyltransferase(s) not fully defined at that time
  8. 2008 High

    Elucidation of the PKCε→14-3-3→PRMT1→exportin-1 nuclear export cascade and the Erk2→p300 acetylation cascade revealed that opposing PTM programs toggle RIP140 between nuclear repressor and cytoplasmic effector states.

    Evidence Sequential mutagenesis, Co-IP of 14-3-3/PRMT1/exportin-1, nuclear/cytoplasmic fractionation, adipocyte rescue assays

    PMID:18628823 PMID:18655826

    Open questions at the time
    • Kinetics and stimulus specificity of export vs. retention decisions not resolved
    • Whether the two cascades are coordinated or independent in vivo unclear
  9. 2009 High

    Demonstration that cytoplasmic RIP140 inhibits GLUT4 trafficking by blocking Akt-mediated AS160 phosphorylation established a non-genomic, insulin-signaling regulatory function for the exported corepressor.

    Evidence Co-IP of RIP140-AS160, GLUT4 trafficking and glucose uptake assays, diet-induced obesity mouse model

    PMID:19945409

    Open questions at the time
    • Structural basis of RIP140-AS160 interaction unknown
    • Relative contribution of nuclear vs. cytoplasmic RIP140 to insulin resistance in vivo not quantified
  10. 2011 High

    Finding that cytoplasmic RIP140 interacts with perilipin on lipid droplets to promote HSL recruitment and lipolysis added a second non-genomic metabolic function, linking RIP140 export to lipid mobilization.

    Evidence Co-IP, lipid droplet fractionation, lipolysis assay, confocal microscopy in adipocytes

    PMID:21504789

    Open questions at the time
    • Signal that triggers RIP140 localization to lipid droplets vs. cytosol not defined
    • Whether lipolysis and GLUT4-inhibitory functions are simultaneous or sequential unknown
  11. 2012 High

    Discovery that LPS/Syk-triggered tyrosine phosphorylation of RIP140 leads to RelA-mediated SCF ubiquitination and degradation, contributing to endotoxin tolerance, connected RIP140 to innate immune regulation beyond metabolism.

    Evidence Co-IP, Syk kinase assay, ubiquitination/degradation assays, non-degradable RIP140 knockin macrophages, endotoxin tolerance model

    PMID:22388040

    Open questions at the time
    • Whether Syk-mediated degradation occurs in non-immune cell types unknown
    • Full repertoire of inflammatory genes controlled by RIP140 not mapped
  12. 2013 High

    Genome-wide ChIP-seq revealed that RIP140 co-occupies >80% of ERα binding sites at H3K4me1-marked enhancers with FOXA1 and GATA3 in breast cancer cells, redefining it as a genome-wide ERα co-regulator rather than a gene-selective modulator.

    Evidence ChIP-seq, siRNA knockdown, gene expression and proliferation analysis in breast cancer cells

    PMID:23404106 PMID:25145671

    Open questions at the time
    • Whether RIP140 acts as coactivator or corepressor at individual ERα enhancers not resolved genome-wide
    • Structural determinants of enhancer selectivity unknown
  13. 2014 High

    Demonstration that RIP140 stimulates APC transcription and inhibits Wnt/β-catenin signaling in intestinal epithelium, and that acetylated RIP140 recruits the SWI/SNF component Brm for chromatin remodeling at pluripotency loci, expanded its mechanistic repertoire to Wnt pathway suppression and developmental chromatin remodeling.

    Evidence Knockout/transgenic mice, reporter assays, ChIP with nucleosome mapping, mutagenesis of acetylation sites

    PMID:24489122 PMID:24667635

    Open questions at the time
    • Whether Wnt pathway repression is nuclear receptor-dependent or independent not fully resolved
    • Brm recruitment mechanism at non-pluripotency targets not tested
  14. 2023 High

    Cardiac-specific Nrip1 deletion showed derepression of ERR/MEF2-dependent enhancers governing mitochondrial and contractile genes, augmented fatty acid oxidation, and protection against pressure-overload heart failure, demonstrating tissue-specific therapeutic potential.

    Evidence Conditional knockout mice (cardiac and striated muscle), genomic enhancer analysis, cardiac metabolic assays, pressure overload model

    PMID:36927960

    Open questions at the time
    • Whether pharmacologic RIP140 inhibition recapitulates genetic deletion in the heart untested
    • Long-term consequences of sustained metabolic derepression in cardiomyocytes unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • No high-resolution structural model of RIP140 exists, and the rules governing its context-dependent switch between corepressor and coactivator function at individual genomic loci remain undefined.
  • No crystal or cryo-EM structure of RIP140 or its complexes
  • Genome-wide classification of loci where RIP140 activates vs. represses not available
  • Relative contribution of nuclear vs. cytoplasmic functions in disease states not quantified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 12 GO:0060090 molecular adaptor activity 4 GO:0098772 molecular function regulator activity 4
Localization
GO:0005634 nucleus 6 GO:0005829 cytosol 4 GO:0005811 lipid droplet 1
Pathway
R-HSA-74160 Gene expression (Transcription) 9 R-HSA-1430728 Metabolism 7 R-HSA-4839726 Chromatin organization 5 R-HSA-1266738 Developmental Biology 4 R-HSA-168256 Immune System 4 R-HSA-1474165 Reproduction 3 R-HSA-162582 Signal Transduction 2
Partners
AS160CTBP1ESR1HDAC3PGC1APPARGRELATAS2R60

Evidence

Reading pass · 42 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 RIP140 (NRIP1) directly interacts in vitro with the ligand-dependent activation domain AF2 of the estrogen receptor; this interaction is enhanced by estrogen but not anti-estrogens, and RIP140 also interacts with estrogen receptor in intact cells to modulate its transcriptional activity. In vitro binding assay, co-immunoprecipitation in intact cells, transient transfection reporter assay The EMBO journal High 7641693
1996 RIP140 contains two distinct binding sites (site 1 and site 2) that independently interact with the ligand-binding domain of the estrogen receptor, thyroid hormone receptor, and retinoic acid receptor; site 1 preferentially mediates interaction with RXR. When fused to a heterologous DNA-binding domain, RIP140 stimulates transcription in yeast and mammalian cells, suggesting it bridges receptors to the basal transcription machinery. In vitro binding assay, GST pulldown, yeast and mammalian reporter assays, mutant receptor analysis Molecular and cellular biology High 8887632
1998 RIP140 interacts with PPARα, PPARγ, and RXR in a ligand-dependent manner and forms ternary complexes with RXR-containing heterodimers in the presence of RXR ligands; RIP140 competes with the coactivator SRC-1 for binding to nuclear receptors and thereby downregulates receptor activity, acting as a competitive inhibitor of coactivation. Yeast two-hybrid, in vitro binding assay, mammalian reporter assay, competition binding Molecular endocrinology High 9626662
1998 Mouse RIP140 functions as a corepressor for the orphan nuclear receptor TR2; the receptor-interacting domains of RIP140 were mapped to regions containing LXXLL motifs, and the RIP140-interacting domain of TR2 was mapped to its C-terminal AF-2 region. RIP140 interaction with TR2 in vivo caused cytosolic TR2-GFP to translocate into the nucleus. Yeast two-hybrid, GAL4 reporter assay, GFP localization, co-immunoprecipitation Molecular and cellular biology High 9774688
1999 RIP140 antagonizes all glucocorticoid receptor (GR)-mediated transcriptional responses (activation and repression) through direct interaction with GR ligand-binding domain (confirmed by GST pulldown); this repression can be partially overcome by overexpression of coactivator TIF2, indicating competition for GR binding. GST pulldown, mammalian reporter assay, competition with TIF2 coactivator The Journal of biological chemistry High 10364267
1999 RIP140 interacts with the Ah receptor (AhR) via the AhR transactivation domain Q-rich subdomain, not through LXXLL motifs; the RIP140 interaction domain for AhR maps to residues 154–350, distinct from the estrogen receptor binding region, and RIP140 enhances TCDD-mediated transcriptional activity. Co-immunoprecipitation, co-localization assay, domain mapping, reporter gene assay The Journal of biological chemistry High 10428779
2000 LXXLL core motif sequences in RIP140 mediate ligand-dependent binding to steroid and retinoid nuclear receptors with defined affinity and selectivity; variant residues at positions -1 and +2 relative to the first conserved leucine influence binding affinity. Peptide inhibition assay, yeast two-hybrid with core LXXLL motif variants The Journal of biological chemistry High 11078741
2000 Nrip1 (RIP140) is essential for ovulation in female mice; null mice are viable but females are completely infertile due to failure of mature follicles to release oocytes, while luteinization proceeds normally. Knockout mouse model, histological analysis, endocrine phenotyping Nature medicine High 11100122
2001 CtBP interacts with RIP140 in vitro and in vivo through the PIDLSCK sequence in the N-terminal region of RIP140; acetylation of Lys in this motif by p300/CBP dramatically reduces CtBP binding and decreases transcriptional repression, providing a mechanism for de-repression of nuclear hormone receptor-regulated genes. Co-immunoprecipitation, in vitro binding assay, acetylation-specific antibody, site-directed mutagenesis, reporter assay Molecular and cellular biology High 11509661
2001 RIP140 forms a ligand-dependent ternary complex with retinoic acid receptor/retinoid X receptor (RAR/RXR) and recruits histone deacetylase 3 (HDAC3) via a novel C-terminal motif (LTKTNPILYYMLQK); this results in decreased histone acetylation on RA response element-containing promoters and suppression of RA-induced gene expression. Deletion of this C-terminal motif abolishes HDAC3 recruitment and repression. Co-immunoprecipitation, chromatin immunoprecipitation (ChIP), site-directed mutagenesis, reporter assay The Journal of biological chemistry High 11278635
2001 14-3-3 proteins interact with RIP140 and can export it from the nucleus, changing its intranuclear localization; this 14-3-3-mediated relocalization of RIP140 enhances glucocorticoid receptor transactivation, identifying cytoplasmic/nuclear shuttling as a regulatory mechanism for RIP140 corepressor activity. Co-immunoprecipitation, colocalization studies/immunofluorescence, transfection reporter assay Molecular endocrinology Medium 11266503
2002 Embryo transfer and ovarian transplantation experiments demonstrate that the ovary is the only site in which RIP140 action is essential for female fertility; if the ovulatory block is bypassed, RIP140-null females can establish and maintain pregnancies. Embryo transfer, ovarian transplantation, genetic rescue experiment Endocrinology High 11796527
2003 RIP140 localizes to small nuclear foci defined by a 40-amino-acid sequence; upon ligand-activated GR binding, both proteins redistribute to large nuclear domains. Full corepressor activity requires both C-terminal receptor-binding LXXLL motifs and interaction with CtBP, and redistribution requires the DNA-binding domain of GR. Fluorescence microscopy, domain deletion analysis, reporter assay, Co-IP Molecular and cellular biology High 12773562
2004 RIP140-null mice are lean, resist high-fat diet-induced obesity, have increased oxygen consumption, and show reduced lipogenic enzyme expression but markedly elevated UCP1 and energy dissipation/mitochondrial uncoupling genes in white adipose tissue, establishing RIP140 as a key transcriptional repressor of fat accumulation and energy expenditure. Knockout mouse model, gene expression analysis, metabolic phenotyping, high-fat diet challenge Proceedings of the National Academy of Sciences High 15155905
2005 RIP140 suppresses oxidative metabolism and mitochondrial biogenesis in adipocytes; siRNA depletion of RIP140 upregulates gene clusters in glycolysis, TCA cycle, fatty acid oxidation, and oxidative phosphorylation, and re-expression restores repression. RIP140 requires ERRα to regulate hexose uptake and mitochondrial proteins SDHB and CoxVb. siRNA knockdown, Affymetrix gene expression profiling, 14C-glucose oxidation assay, oxygen consumption measurement, mouse embryonic fibroblast rescue experiment The Journal of clinical investigation High 16374519
2005 RIP140 is essential for ovulation; in the absence of RIP140, cumulus expansion is reduced, oocyte detachment from the mural cell wall is impaired, and follicles fail to rupture in response to LH, due to aberrant expression of genes encoding signaling pathway components and extracellular matrix proteins. Knockout mouse model, hormonal stimulation, histological analysis, gene expression profiling Endocrinology High 15919748
2005 MAPK-mediated phosphorylation of RIP140 at Thr202 and Thr207 in the N-terminal repression domain enhances its transcriptional co-repressive activity by increasing recruitment of histone deacetylases; mutations mimicking dephosphorylation impair HDAC recruitment and repressive activity, while phospho-mimetic mutations render RIP140 a more potent repressor. Mass spectrometry (phosphoproteomics), site-directed mutagenesis, HDAC recruitment assay, reporter assay, MAPK inhibitor treatment Molecular & cellular proteomics High 16093479
2007 RIP140 is a key regulator of skeletal muscle oxidative metabolism; low RIP140 levels promote oxidative fiber formation while increased expression suppresses it. In the absence of RIP140, genes for fatty acid oxidation, oxidative phosphorylation, and mitochondrial biogenesis are upregulated, with effects intrinsic to muscle cells. Knockout, heterozygous, and transgenic mouse models; expression profiling; cultured myofiber analysis Cell metabolism High 17767910
2007 Pyridoxal 5'-phosphate (PLP/vitamin B6) conjugates RIP140 at Lys613, enhancing its transcriptional corepressive activity by increasing interaction with histone deacetylases and promoting nuclear retention. LC-ESI-MS/MS mapping of modification site, in vitro binding assay for HDAC interaction, nuclear fractionation, adipocyte differentiation functional assay Nature chemical biology High 17277785
2007 RIP140 is required for both DNA methylation and histone methylation to silence Ucp1 in white adipocytes; RIP140 expression promotes assembly of DNA and histone methyltransferases on the Ucp1 enhancer, leading to methylation of specific CpGs and histones, acting as a scaffold for epigenetic repression. Chromatin immunoprecipitation, bisulfite genomic sequencing, methyltransferase recruitment analysis The EMBO journal High 17972916
2007 RIP140 is differentially recruited to the TR2 promoter via a GRIP1 platform molecule in differentiated vs. undifferentiated adipocytes; in differentiated cells, RA triggers recruitment of a HDAC-containing GRIP1/RIP140 complex (vs. PCAF coactivator complex in undifferentiated cells). GRIP1 interacts directly with RIP140 through its C-terminal AD2 domain. Co-immunoprecipitation, chromatin immunoprecipitation, reporter assay, domain mapping Nucleic acids research High 17389641
2008 PKCε-mediated phosphorylation of RIP140 at Ser102 and Ser1003 promotes direct binding of 14-3-3, which recruits protein arginine methyltransferase 1 (PRMT1) to methylate RIP140; methylated RIP140 then preferentially recruits exportin 1 for nuclear export, thereby reducing its nuclear gene-repressive activity. The phosphorylation-deficient mutant that stays in the nucleus is more effective at rescuing fat accumulation in RIP140-null adipocytes. Mutagenesis, Co-immunoprecipitation, nuclear/cytoplasmic fractionation, adipocyte differentiation rescue experiment PloS one High 18628823
2008 RIP140 directly interacts with PGC-1α and suppresses its transcriptional activating activity; both proteins regulate CIDEA expression through binding of ERRα and NRF-1 to the CIDEA promoter, providing a nuclear receptor-dependent and -independent mechanism for antagonism. Co-immunoprecipitation, chromatin immunoprecipitation, reporter assay, overexpression/knockdown Molecular and cellular biology High 18794372
2008 SUMOylation of RIP140 at Lys756 (in RD3) and Lys1154 (in RD4) by SUMO-1 is required for full transcriptional repressor function; mutation of these SUMOylation sites compromised RIP140 repressor activity and ability to repress ERα-dependent transcription. SUMO-1 conjugation also influences subnuclear distribution of RIP140. Site-directed mutagenesis, reporter assay, subnuclear localization analysis, in vivo SUMOylation assay The Journal of biological chemistry High 18211901
2008 Erk2 phosphorylates RIP140 at Thr202/Thr207, which promotes recruitment of p300 for subsequent lysine acetylation at Lys158/Lys287; this sequential phosphorylation-acetylation cascade enhances RIP140 gene-repressive activity and fat accumulation in adipocytes. p300 was identified as the specific acetyltransferase for RIP140 in vivo. In vivo kinase assay, site-directed mutagenesis, Co-immunoprecipitation, adipocyte differentiation rescue assay Cellular signalling High 18655826
2009 Cytoplasmic RIP140 (exported after PKCε phosphorylation and arginine methylation) interacts with the Akt substrate AS160, preventing its phosphorylation by Akt, which in turn reduces GLUT4 trafficking to the plasma membrane and impairs insulin-stimulated glucose uptake in adipocytes. Co-immunoprecipitation, GLUT4 trafficking assay, glucose uptake assay, PKCε activation, diet-induced obesity mouse model Cell metabolism High 19945409
2009 RIP140 mediates thyroid hormone (T3) repression of the Crabp1 gene during adipocyte differentiation by replacing coactivators GRIP1 and PCAF on the basal promoter and forming a repressive complex with CtBP1, HDAC3, and G9a; this is accompanied by chromatin changes including nucleosome repositioning, loss of active marks (H3-Ac, H3K4-me3) and gain of repressive marks (H3K9-me3, H3K27-me3). Chromatin immunoprecipitation, chromatin remodeling analysis, reporter assay Nucleic acids research High 19778926
2010 RIP140 directly interacts with E2F1 (confirmed by GST pulldown and Co-IP) and represses E2F1 transactivation of target promoters including CCNE1 and CCNB2; overexpression of RIP140 reduces the proportion of cells in S phase. GST pulldown, co-immunoprecipitation, chromatin immunoprecipitation, reporter assay, flow cytometry cell cycle analysis Clinical cancer research High 20410059
2011 Cytoplasmic RIP140 directly interacts with perilipin on lipid droplets; this interaction promotes more efficient recruitment of hormone-sensitive lipase (HSL) and facilitates ATGL/CGI-58 complex formation, ultimately enhancing lipolysis in adipocytes. Elevated diacylglycerol levels trigger RIP140 cytoplasmic accumulation. Co-immunoprecipitation, lipid droplet fractionation, lipolysis assay, confocal microscopy Cellular signalling High 21504789
2011 Cytoplasmic RIP140 interacts with AS160 to regulate adiponectin vesicle secretion; knockdown of RIP140 or its nuclear export trigger PKCε promotes adiponectin secretion without affecting production or oligomerization. Co-immunoprecipitation, adiponectin secretion assay, PKCε knockdown, conditioned media functional assay Cellular signalling Medium 21872658
2012 LPS stimulation triggers Syk kinase-mediated tyrosine phosphorylation of RIP140, which enables interaction with NF-κB subunit RelA; RelA then acts as an adaptor to recruit the E3 ligase SCF, which degrades RIP140, resulting in inactivation of inflammatory cytokine genes and contributing to endotoxin tolerance. Co-immunoprecipitation, kinase assay (Syk), ubiquitination/degradation assay, macrophage knockin of non-degradable RIP140, endotoxin tolerance assay Nature immunology High 22388040
2012 RIP140 interacts with the NF-κB subunit p65 (RelA) to coactivate inflammatory cytokine gene expression in cardiomyocytes; p65 knockdown reverses RIP140-mediated induction of proinflammatory genes, and p65 is also required for RIP140-mediated repression of metabolic gene expression in these cells. Co-immunoprecipitation, reporter assay, siRNA knockdown, gene expression analysis Archives of biochemistry and biophysics Medium 24823858
2013 RIP140 is required for ERα complex formation and ERα-mediated gene expression in breast cancer; ChIP-seq shows RIP140 shares >80% of its binding sites with ERα, colocalizing at H3K4me1-marked enhancer regions with FOXA1, GATA3, p300, CBP, and p160 family members. ChIP-seq, siRNA knockdown, gene expression analysis, cell proliferation assay Cancer research High 25145671
2013 RIP140 acts as a co-regulator with ERα to directly regulate expression of amphiregulin (Areg), progesterone receptor (Pgr), and Stat5a in the mammary gland; RIP140 is required in both epithelial and stromal compartments for ductal elongation. ChIP-seq, tissue recombination experiments, knockout and transgenic mouse models, gene expression analysis Development High 23404106
2014 RIP140 stimulates APC transcription and inhibits β-catenin activation and Wnt target gene expression in intestinal epithelial cells; RIP140-null mice show altered intestinal homeostasis, while RIP140 overexpression represses colon cancer cell proliferation. Knockout and transgenic mouse models, reporter assay, Co-IP, gene expression analysis, xenograft assay The Journal of clinical investigation High 24667635
2014 In RA-induced embryonic stem cell differentiation, RIP140 coordinates repressive chromatin remodeling of Nanog and Oct4 gene loci; this requires RARα, RIP140, and Brm (SWI/SNF). Lysine acetylation of RIP140 is critical for its ability to recruit Brm to these loci. Chromatin immunoprecipitation, nucleosome mapping, siRNA knockdown, mutagenesis of acetylation sites Nucleic acids research High 24489122
2014 RIP140 enhances macrophage-derived foam cell formation by repressing expression of reverse cholesterol transport genes ABCA1 and ABCG1; macrophage-specific RIP140 knockdown in ApoE-null mice ameliorates high-cholesterol diet-induced atherosclerosis. Gene knockdown in macrophages, gene expression analysis, bone marrow transplant mouse model, atherosclerosis quantification Journal of molecular and cellular cardiology High 25528964
2016 RIP140 interacts with DNMT3b in macrophages; LPS-induced RIP140 promotes DNMT3b-mediated methylation of the PPARγ promoter, silencing PPARγ transcription and amplifying inflammation. RIP140 knockdown reduces PPARγ promoter methylation and restores PPARγ activity. Co-immunoprecipitation, bisulfite pyrosequencing, PPARγ promoter activity assay, siRNA knockdown, DNMT3b activity assay Pulmonary pharmacology & therapeutics Medium 26921464
2017 RIP140 in osteoclast precursors forms a transcription-suppressor complex with orphan nuclear receptor TR4 (testicular receptor 4) to repress osteoclastogenic genes; macrophage-specific RIP140 knockdown in mice leads to increased osteoclast differentiation and bone resorption. Syk-stimulated RIP140 degradation terminates this suppressive activity. Macrophage-specific transgenic knockdown, bone marrow transplantation, Co-immunoprecipitation, gene expression analysis, Syk kinase assay JCI insight High 28405613
2018 Glyburide activates CaMKII, which triggers specific ubiquitination and proteasomal degradation of RIP140 in macrophages, enhancing M2 polarization and anti-inflammatory response; this mechanism contributes to wound healing. RIP140 degradation assay, CaMKII inhibitor, ubiquitination assay, macrophage polarization assay, wound healing mouse model Scientific reports Medium 29339732
2022 RIP140 inhibits breast cancer cell glycolysis and proliferation by repressing GLUT3 transcription through inhibition of HIF-2α transcriptional activity, in cooperation with p53; RIP140-deficiency causes a glycolysis-dependent increase in tumor growth. Cell proliferation assay, metabolic assay (glycolysis), reporter assay, siRNA knockdown, co-regulator interaction analysis Cellular and molecular life sciences Medium 35501580
2023 Cardiac-specific or striated muscle-specific deletion of RIP140 (Nrip1) in mice increases expression of genes for mitochondrial energy metabolism and contractile function via activation of genomic enhancers enriched in ERR and MEF2 binding motifs, augments fatty acid oxidation and triacylglyceride turnover, and protects against pressure overload-induced heart failure. Conditional knockout mouse models (strNrip1-/- and csNrip1-/-), genomic enhancer analysis, cardiac metabolic assays, pressure overload model The Journal of clinical investigation High 36927960

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1995 Nuclear factor RIP140 modulates transcriptional activation by the estrogen receptor. The EMBO journal 663 7641693
2004 Nuclear receptor corepressor RIP140 regulates fat accumulation. Proceedings of the National Academy of Sciences of the United States of America 312 15155905
2008 Chloroplastic protein NRIP1 mediates innate immune receptor recognition of a viral effector. Cell 286 18267075
2005 Suppression of oxidative metabolism and mitochondrial biogenesis by the transcriptional corepressor RIP140 in mouse adipocytes. The Journal of clinical investigation 191 16374519
1998 A regulatory role for RIP140 in nuclear receptor activation. Molecular endocrinology (Baltimore, Md.) 190 9626662
2007 The transcriptional corepressor RIP140 regulates oxidative metabolism in skeletal muscle. Cell metabolism 164 17767910
2000 The nuclear receptor co-repressor nrip1 (RIP140) is essential for female fertility. Nature medicine 153 11100122
2008 A functional interaction between RIP140 and PGC-1alpha regulates the expression of the lipid droplet protein CIDEA. Molecular and cellular biology 136 18794372
2000 Core LXXLL motif sequences in CREB-binding protein, SRC1, and RIP140 define affinity and selectivity for steroid and retinoid receptors. The Journal of biological chemistry 136 11078741
2001 Acetylation of nuclear hormone receptor-interacting protein RIP140 regulates binding of the transcriptional corepressor CtBP. Molecular and cellular biology 126 11509661
1999 Differential recruitment of coactivator RIP140 by Ah and estrogen receptors. Absence of a role for LXXLL motifs. The Journal of biological chemistry 121 10428779
1996 RIP-140 interacts with multiple nuclear receptors by means of two distinct sites. Molecular and cellular biology 116 8887632
1998 Cloning and characterization of mouse RIP140, a corepressor for nuclear orphan receptor TR2. Molecular and cellular biology 113 9774688
2015 miR-30 promotes thermogenesis and the development of beige fat by targeting RIP140. Diabetes 111 25576051
2006 Metabolic regulation by the nuclear receptor corepressor RIP140. Trends in endocrinology and metabolism: TEM 91 16815031
2007 RIP140 directs histone and DNA methylation to silence Ucp1 expression in white adipocytes. The EMBO journal 89 17972916
2012 NF-κB-mediated degradation of the coactivator RIP140 regulates inflammatory responses and contributes to endotoxin tolerance. Nature immunology 88 22388040
1999 Receptor interacting protein RIP140 inhibits both positive and negative gene regulation by glucocorticoids. The Journal of biological chemistry 86 10364267
2013 Distinct functions for RIP140 in development, inflammation, and metabolism. Trends in endocrinology and metabolism: TEM 66 23742741
2007 Vitamin B6 conjugation to nuclear corepressor RIP140 and its role in gene regulation. Nature chemical biology 63 17277785
2001 Regulation of glucocorticoid receptor activity by 14--3-3-dependent intracellular relocalization of the corepressor RIP140. Molecular endocrinology (Baltimore, Md.) 62 11266503
2007 Role of RIP140 in metabolic tissues: connections to disease. FEBS letters 54 18023280
1999 Estrogen receptor domains E and F: role in dimerization and interaction with coactivator RIP-140. Molecular endocrinology (Baltimore, Md.) 54 9973258
2020 Circular RNA circNTRK2 facilitates the progression of esophageal squamous cell carcinoma through up-regulating NRIP1 expression via miR-140-3p. Journal of experimental & clinical cancer research : CR 53 32653032
2006 RIP140 expression is stimulated by estrogen-related receptor alpha during adipogenesis. The Journal of biological chemistry 52 16923809
2001 Transcriptional activation of the nuclear receptor corepressor RIP140 by retinoic acid: a potential negative-feedback regulatory mechanism. Biochemical and biophysical research communications 51 11467847
2008 RNAi screens reveal novel metabolic regulators: RIP140, MAP4k4 and the lipid droplet associated fat specific protein (FSP) 27. Acta physiologica (Oxford, England) 50 18171433
2009 A negative regulatory pathway of GLUT4 trafficking in adipocyte: new function of RIP140 in the cytoplasm via AS160. Cell metabolism 48 19945409
2000 Environmental estrogens induce transcriptionally active estrogen receptor dimers in yeast: activity potentiated by the coactivator RIP140. Environmental health perspectives 48 10656848
2014 NRIP1/RIP140 siRNA-mediated attenuation counteracts mitochondrial dysfunction in Down syndrome. Human molecular genetics 47 24698981
2010 The transcriptional coregulator RIP140 represses E2F1 activity and discriminates breast cancer subtypes. Clinical cancer research : an official journal of the American Association for Cancer Research 46 20410059
2006 Transcriptional regulation of the human NRIP1/RIP140 gene by estrogen is modulated by dioxin signalling. Molecular pharmacology 46 16391242
2003 Regulation of subnuclear localization is associated with a mechanism for nuclear receptor corepression by RIP140. Molecular and cellular biology 46 12773562
2018 CRISPR-delivery particles targeting nuclear receptor-interacting protein 1 (Nrip1) in adipose cells to enhance energy expenditure. The Journal of biological chemistry 44 30190322
2014 Reducing RIP140 expression in macrophage alters ATM infiltration, facilitates white adipose tissue browning, and prevents high-fat diet-induced insulin resistance. Diabetes 44 24969109
2013 The transcriptional co-factor RIP140 regulates mammary gland development by promoting the generation of key mitogenic signals. Development (Cambridge, England) 44 23404106
2010 Role of nuclear receptor corepressor RIP140 in metabolic syndrome. Biochimica et biophysica acta 44 21193034
2006 The nuclear receptor transcriptional coregulator RIP140. Nuclear receptor signaling 44 17088940
2006 Negative regulation of hormone signaling by RIP140. The Journal of steroid biochemistry and molecular biology 43 17056252
2014 RIP140 increases APC expression and controls intestinal homeostasis and tumorigenesis. The Journal of clinical investigation 42 24667635
2001 Ligand-dependent formation of retinoid receptors, receptor-interacting protein 140 (RIP140), and histone deacetylase complex is mediated by a novel receptor-interacting motif of RIP140. The Journal of biological chemistry 42 11278635
2008 SUMOylation modulates the transcription repressor function of RIP140. The Journal of biological chemistry 40 18211901
2005 Role of the RIP140 corepressor in ovulation and adipose biology. The Journal of endocrinology 39 15817822
2005 Regulation of co-repressive activity of and HDAC recruitment to RIP140 by site-specific phosphorylation. Molecular & cellular proteomics : MCP 39 16093479
2012 Roles of transcriptional corepressor RIP140 and coactivator PGC-1α in energy state of chronically infarcted rat hearts and mitochondrial function of cardiomyocytes. Molecular and cellular endocrinology 38 22503866
2014 RIP140 represses the "brown-in-white" adipocyte program including a futile cycle of triacylglycerol breakdown and synthesis. Molecular endocrinology (Baltimore, Md.) 37 24479876
2021 CircRNA NRIP1 promotes papillary thyroid carcinoma progression by sponging mir-195-5p and modulating the P38 MAPK and JAK/STAT pathways. Diagnostic pathology 36 34689819
2020 circ-NRIP1 Promotes Glycolysis and Tumor Progression by Regulating miR-186-5p/MYH9 Axis in Gastric Cancer. Cancer management and research 36 32765095
2008 Post-translational modifications of nuclear co-repressor RIP140: a therapeutic target for metabolic diseases. Current medicinal chemistry 35 18288993
2008 Modulation of lysine acetylation-stimulated repressive activity by Erk2-mediated phosphorylation of RIP140 in adipocyte differentiation. Cellular signalling 34 18655826
2022 Fusion gene detection by RNA-sequencing complements diagnostics of acute myeloid leukemia and identifies recurring NRIP1-MIR99AHG rearrangements. Haematologica 33 34134471
2015 Suppressing NRIP1 inhibits growth of breast cancer cells in vitro and in vivo. Oncotarget 33 26492163
2013 Negative regulation of estrogen signaling by ERβ and RIP140 in ovarian cancer cells. Molecular endocrinology (Baltimore, Md.) 33 23885094
2011 Aryl hydrocarbon receptor modulation of estrogen receptor α-mediated gene regulation by a multimeric chromatin complex involving the two receptors and the coregulator RIP140. Toxicological sciences : an official journal of the Society of Toxicology 33 22071320
2009 Four and a half LIM domains 1 (FHL1) and receptor interacting protein of 140kDa (RIP140) interact and cooperate in estrogen signaling. The international journal of biochemistry & cell biology 33 19401155
2023 ALKBH5-induced circular RNA NRIP1 promotes glycolysis in thyroid cancer cells by targeting PKM2. Cancer science 32 36851875
2011 Clenbuterol, a β2-adrenergic agonist, reciprocally alters PGC-1 alpha and RIP140 and reduces fatty acid and pyruvate oxidation in rat skeletal muscle. American journal of physiology. Regulatory, integrative and comparative physiology 32 22071161
2008 PKCepsilon stimulated arginine methylation of RIP140 for its nuclear-cytoplasmic export in adipocyte differentiation. PloS one 31 18628823
2003 Negative feedback at the level of nuclear receptor coregulation. Self-limitation of retinoid signaling by RIP140. The Journal of biological chemistry 31 14506269
2018 MicroRNA-548-3p and MicroRNA-576-5p enhance the migration and invasion of esophageal squamous cell carcinoma cells via NRIP1 down-regulation. Neoplasma 30 29940757
2006 Multilocus analysis of estrogen-related genes in Spanish postmenopausal women suggests an interactive role of ESR1, ESR2 and NRIP1 genes in the pathogenesis of osteoporosis. Bone 30 16530497
2005 Multiple signaling defects in the absence of RIP140 impair both cumulus expansion and follicle rupture. Endocrinology 30 15919748
2021 circ_NRIP1 is oncogenic in malignant development of esophageal squamous cell carcinoma (ESCC) via miR-595/SEMA4D axis and PI3K/AKT pathway. Cancer cell international 29 33957921
2012 Absence of RIP140 reveals a pathway regulating glut4-dependent glucose uptake in oxidative skeletal muscle through UCP1-mediated activation of AMPK. PloS one 29 22389706
2011 Cytoplasmic receptor-interacting protein 140 (RIP140) interacts with perilipin to regulate lipolysis. Cellular signalling 28 21504789
2015 NOP14 suppresses breast cancer progression by inhibiting NRIP1/Wnt/β-catenin pathway. Oncotarget 27 26213846
2000 The impact of differential binding of wild-type RARalpha, PML-, PLZF- and NPM-RARalpha fusion proteins towards transcriptional co-activator, RIP-140, on retinoic acid responses in acute promyelocytic leukemia. Leukemia 27 10637480
2014 Complex formation and function of estrogen receptor α in transcription requires RIP140. Cancer research 26 25145671
2007 Selective repression of retinoic acid target genes by RIP140 during induced tumor cell differentiation of pluripotent human embryonal carcinoma cells. Molecular cancer 26 17880687
2002 Embryo transfer experiments and ovarian transplantation identify the ovary as the only site in which nuclear receptor interacting protein 1/RIP140 action is crucial for female fertility. Endocrinology 26 11796527
2009 RIP140 in thyroid hormone-repression and chromatin remodeling of Crabp1 gene during adipocyte differentiation. Nucleic acids research 25 19778926
2007 Orphan nuclear receptor TR2, a mediator of preadipocyte proliferation, is differentially regulated by RA through exchange of coactivator PCAF with corepressor RIP140 on a platform molecule GRIP1. Nucleic acids research 25 17389641
2005 Limiting effects of RIP140 in estrogen signaling: potential mediation of anti-estrogenic effects of retinoic acid. The Journal of biological chemistry 25 15632153
2018 Glyburide and retinoic acid synergize to promote wound healing by anti-inflammation and RIP140 degradation. Scientific reports 22 29339732
2015 Expression and role of RIP140/NRIP1 in chronic lymphocytic leukemia. Journal of hematology & oncology 22 25879677
2012 The RIP140 gene is a transcriptional target of E2F1. PloS one 22 22629304
2017 Transcriptional coregulator RIP140: an essential regulator of physiology. Journal of molecular endocrinology 21 28073818
2015 The emerging role of the transcriptional coregulator RIP140 in solid tumors. Biochimica et biophysica acta 21 26116758
2014 RIP140 contributes to foam cell formation and atherosclerosis by regulating cholesterol homeostasis in macrophages. Journal of molecular and cellular cardiology 21 25528964
2004 Retinoids and receptor interacting protein 140 (RIP140) in gene regulation. Current medicinal chemistry 21 15180561
2003 Effects of retinoid ligands on RIP140: molecular interaction with retinoid receptors and biological activity. Biochemistry 21 12549917
2021 Hyperoside Protects HK-2 Cells Against High Glucose-Induced Apoptosis and Inflammation via the miR-499a-5p/NRIP1 Pathway. Pathology oncology research : POR 20 34257594
2016 Overexpression and potential roles of NRIP1 in psoriasis. Oncotarget 20 27708240
2006 The nuclear receptor co-repressor RIP140 controls the expression of metabolic gene networks. Biochemical Society transactions 20 17073760
2019 The circular RNA-NRIP1 plays oncogenic roles by targeting microRNA-505 in the renal carcinoma cell lines. Journal of cellular biochemistry 19 31692056
2014 Coordinated repressive chromatin-remodeling of Oct4 and Nanog genes in RA-induced differentiation of embryonic stem cells involves RIP140. Nucleic acids research 19 24489122
2014 The p65 subunit of NF-κB involves in RIP140-mediated inflammatory and metabolic dysregulation in cardiomyocytes. Archives of biochemistry and biophysics 19 24823858
2011 Negative regulation of adiponectin secretion by receptor interacting protein 140 (RIP140). Cellular signalling 19 21872658
2004 Molecular interaction of retinoic acid receptors with coregulators PCAF and RIP140. Molecular and cellular endocrinology 19 15489004
2023 RIP140 deficiency enhances cardiac fuel metabolism and protects mice from heart failure. The Journal of clinical investigation 18 36927960
2022 RIP140 inhibits glycolysis-dependent proliferation of breast cancer cells by regulating GLUT3 expression through transcriptional crosstalk between hypoxia induced factor and p53. Cellular and molecular life sciences : CMLS 18 35501580
2017 RIP140 in monocytes/macrophages regulates osteoclast differentiation and bone homeostasis. JCI insight 18 28405613
2015 M1-M2 balancing act in white adipose tissue browning - a new role for RIP140. Adipocyte 18 26167418
2011 Reductions in RIP140 are not required for exercise- and AICAR-mediated increases in skeletal muscle mitochondrial content. Journal of applied physiology (Bethesda, Md. : 1985) 18 21700896
2003 Characterization of receptor-interacting protein RIP140 in the regulation of SF-1 responsive target genes. Molecular and cellular endocrinology 18 12782406
2018 Deletion of Nrip1 Extends Female Mice Longevity, Increases Autophagy, and Delays Cell Senescence. The journals of gerontology. Series A, Biological sciences and medical sciences 17 29346516
2016 RIP140 down-regulation alleviates acute lung injury via the inhibition of LPS-induced PPARγ promoter methylation. Pulmonary pharmacology & therapeutics 17 26921464
2014 Downregulation of RIP140 in hepatocellular carcinoma promoted the growth and migration of the cancer cells. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 17 25391428
2017 Overexpression of RIP140 suppresses the malignant potential of hepatocellular carcinoma by inhibiting NF‑κB‑mediated alternative polarization of macrophages. Oncology reports 16 28393222
2017 Transcriptional co-regulator RIP140: An important mediator of the inflammatory response and its associated diseases (Review). Molecular medicine reports 15 28586037