Affinage

ESRRA

Steroid hormone receptor ERR1 · UniProt P11474

Length
423 aa
Mass
45.5 kDa
Annotated
2026-06-09
100 papers in source corpus 51 papers cited in narrative 51 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 10/10 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ERRα (ESRRA) is a ligand-independent orphan nuclear receptor that serves as a master transcriptional regulator of mitochondrial biogenesis, oxidative metabolism, and energy homeostasis, functioning downstream of and in complex with the PGC-1α/PGC-1β coactivators (PMID:15337744, PMID:15087503). Structurally, its ligand-binding domain adopts a transcriptionally active conformation in the absence of ligand because bulky side chains (notably Phe328) occupy the pocket, while an inverted LXXLL motif of PGC-1α docks onto the LBD surface to drive activation (PMID:15337744). ERRα is itself a downstream effector required for PGC-1α-induced mitochondrial gene expression and mtDNA replication, and it autoregulates its own promoter through a dedicated response element while synergizing with PGC-1α (PMID:15087503, PMID:14978033). Through co-occupancy of target promoters it directs broad metabolic programs — fatty acid oxidation, OXPHOS, TCA cycle, mitochondrial fusion/dynamics, and creatine handling — in cardiac, skeletal muscle, hepatic, renal, and intestinal tissues, with in vivo loss producing bioenergetic failure under stress (PMID:17618854, PMID:25624346, PMID:33301705, PMID:15961417). ERRα also drives autophagy by transcriptionally inducing Atg genes and operating in a feed-forward loop with SIRT1 to deacetylate ATG5/BECN1/ATG7, supporting antimicrobial defense and intestinal homeostasis (PMID:28841353, PMID:33172329). Its protein level is a central control node, stabilized or destabilized by an array of factors including the GSK3β/FBXW7 axis downstream of insulin, the E3 ligases RBBP6 and STUB1, FBXL10, LSD1, and parkin (PMID:35440636, PMID:39441040, PMID:31907393, PMID:33450359, PMID:29190800). Cholesterol acts as an endogenous LBD agonist that couples sterol status to ERRα activity in bone and cellular senescence (PMID:26777690, PMID:38216569). Beyond metabolism, ERRα represses TLR-induced inflammation via transcription of the A20 deubiquitinase Tnfaip3 (PMID:26200012) and inhibits type I interferon production by associating with TBK1 and IRF3 to block their complex formation in a transcription-independent manner (PMID:28591144). In cancer, ERRα co-occupies the ERBB2 amplicon with PGC-1β, drives metabolic adaptations underlying lapatinib resistance, and reprograms epigenetic and steroidogenic programs, including switching LSD1 substrate specificity to H3K9 demethylation to promote invasion (PMID:20961995, PMID:27402251, PMID:28348226). A coding ESRRA mutation that decreases its transcriptional activity, together with HDAC4, defines an ESRRA-HDAC4 transcriptional axis linked to a human familial phenotype (PMID:24216484).

Mechanistic history

Synthesis pass · year-by-year structured walk · 21 steps
  1. 1997 Medium

    Establishing the genomic structure and a first functional readout addressed where ERRα resides and whether it modulates estrogen-responsive transcription.

    Evidence FISH mapping, gene cloning, and lactoferrin promoter reporter assays in endometrial carcinoma cells

    PMID:9286700

    Open questions at the time
    • No endogenous physiological target genes defined
    • Coactivator dependence not yet established
  2. 2004 High

    Crystallography resolved how an orphan receptor activates transcription without a ligand, explaining its constitutive activity and coactivator recruitment mode.

    Evidence X-ray structure of the LBD bound to a PGC-1α peptide at 2.5 Å with binding affinity assays

    PMID:15337744

    Open questions at the time
    • Did not exclude endogenous regulatory ligands later shown to exist
    • No genome-wide target context
  3. 2004 High

    Placing ERRα as the effector of PGC-1α-driven mitochondrial biogenesis and demonstrating promoter autoregulation defined the core transcriptional circuit of energy metabolism.

    Evidence Dominant-negative/constitutively active ERRα, mtDNA quantification, ChIP, and reporter assays in fibroblasts

    PMID:14978033 PMID:15087503

    Open questions at the time
    • Tissue-specific target repertoires not resolved
    • Upstream signals controlling the axis unknown
  4. 2004 High

    Knockout phenotypes linked ERRα to specific metabolic targets, showing it directly regulates intestinal lipid handling.

    Evidence ERRα knockout mice, apoA-IV promoter assays, and enterocyte β-oxidation assays

    PMID:15466464

    Open questions at the time
    • Whether the same target set operates in other tissues unaddressed
  5. 2007 High

    In vivo bioenergetic profiling established that ERRα is required for cardiac metabolic adaptation to stress, not just baseline metabolism.

    Evidence ERRα knockout mice with pressure overload, 31P-NMR, and mitochondrial respiration assays

    PMID:17618854

    Open questions at the time
    • Redundancy with ERRγ not yet tested
    • Direct cardiac target genes only partially defined
  6. 2011 High

    Genome-wide mapping integrated ERRα into the circadian clock, revealing reciprocal regulatory loops governing daily metabolic rhythms.

    Evidence ChIP-seq for ERRα/PROX1/BMAL1 in liver plus ERRα-null and Clock mutant phenotyping

    PMID:21731503

    Open questions at the time
    • Mechanism of PROX1 corepression not fully resolved
  7. 2013 High

    Connecting mTOR to ERRα through proteasomal control positioned ERRα as a degradation-regulated node in hepatic lipid metabolism.

    Evidence ChIP-seq in mouse liver, genetic ERRα ablation, rapamycin treatment, and metabolite analysis

    PMID:23562079

    Open questions at the time
    • Specific E3 ligase not identified in this study
    • Direct mTOR-ERRα biochemical link inferred via UPS transcription
  8. 2013 Medium

    A reciprocal interaction with HDAC4 and a hypomorphic human ESRRA mutation defined a transcriptional regulatory axis with disease relevance.

    Evidence Reciprocal co-IP in HeLa cells and mouse cortex, transcriptional activity assays, and family exome sequencing

    PMID:24216484

    Open questions at the time
    • Causal disease mechanism of the variant not fully established
    • Single-lab functional characterization
  9. 2015 High

    Double-knockout genetics revealed functional redundancy and the breadth of cardiac targets ERRs control, extending the program to contraction and conduction genes.

    Evidence ERRα/ERRγ double-knockout mice with cardiac phenotyping and target gene analysis

    PMID:25624346

    Open questions at the time
    • Relative contribution of each receptor to individual targets not dissected
  10. 2015 High

    Identifying direct ERRα binding to inflammatory and sirtuin target promoters extended its role beyond metabolism into innate immune restraint.

    Evidence ERRα knockout macrophages, ChIP at Tnfaip3, NF-κB acetylation, NAD+ quantification, and metabolic flux analysis

    PMID:26200012 PMID:26421366

    Open questions at the time
    • Whether immune effects are separable from metabolic effects not fully resolved
  11. 2016 High

    Discovery of cholesterol as an endogenous LBD agonist reframed ERRα from a strictly ligand-independent receptor to a sterol-responsive one with pharmacological relevance in bone.

    Evidence Affinity chromatography of tissue lipidomes with the LBD, transcriptional assays, and ERRα knockout osteoclastogenesis/bone models

    PMID:26777690

    Open questions at the time
    • Structural mode of cholesterol binding within the occluded pocket not defined
  12. 2016 High

    Linking ERRα to cancer drug resistance and metabolic reprogramming established it as a therapeutic target through inverse agonism.

    Evidence Protein stability assays, glutamine/ROS metabolic profiling, and ERRα inverse agonist in HER2 mouse tumors; AMPK/one-carbon metabolism ChIP-seq with methotrexate sensitivity

    PMID:26804918 PMID:27402251

    Open questions at the time
    • Generality across tumor types not established
  13. 2017 High

    Two transcription-independent mechanisms — substrate-switching of LSD1 and inhibition of TBK1-IRF3 — revealed non-canonical functions distinct from classic coactivator-driven transcription.

    Evidence In vitro reconstitution of LSD1 H3K9 demethylation with invasion assays; co-IP of TBK1-ERRα-IRF3 with IRF3 phosphorylation/dimerization assays in knockout mice

    PMID:28348226 PMID:28591144

    Open questions at the time
    • How ERRα toggles between transcriptional and non-transcriptional modes unknown
  14. 2017 High

    Defining ERRα's role in autophagosome formation through both Atg gene transcription and SIRT1-mediated deacetylation established a dual transcriptional/post-translational control of autophagy.

    Evidence ESRRA knockout macrophages, Atg promoter ChIP, SIRT1 deacetylation assays, and mycobacterial infection/autophagy flux

    PMID:28841353

    Open questions at the time
    • Relative weight of transcriptional versus post-translational arms not quantified
  15. 2017 Medium

    Identifying LSD1 as a demethylase-independent stabilizer of ERRα protein opened a series of studies on post-translational control of ERRα abundance.

    Evidence Ubiquitination assays with LSD1 demethylase-dead mutants and protein stability measurement in breast cancer cells

    PMID:29190800

    Open questions at the time
    • E3 ligase opposing LSD1 not identified here
    • Single-lab study
  16. 2018 High

    ERRα was shown to mediate thyroid-hormone-induced mitochondrial biogenesis, fission, and mitophagy by inducing ULK1, integrating endocrine signaling with mitochondrial quality control.

    Evidence Transcriptomics, ChIP-seq, siRNA of ESRRA/ULK1/DRP1/FUNDC1, and mitophagy/OXPHOS assays

    PMID:29945885

    Open questions at the time
    • Direct ERRα occupancy at all fission/mitophagy effector genes not fully mapped
  17. 2018 Medium

    Characterizing PERM1 as a physical ERRα partner that activates ERR target promoters identified a new cardiac coactivator working alongside PGC-1α.

    Evidence Reciprocal co-IP, one-hybrid and reporter assays, and Perm1 knockout cardiac phenotyping

    PMID:36419485

    Open questions at the time
    • Structural basis of PERM1-ERRα interaction undefined
    • Single-lab study
  18. 2020 High

    Single-cell analysis revealed ERRα couples metabolism to cell-type differentiation in the kidney, broadening its role beyond pure bioenergetics.

    Evidence scRNA-seq, trajectory analysis, ERRα knockout kidney disease models, and patient sample validation

    PMID:33301705

    Open questions at the time
    • Direct differentiation target genes only partially defined
  19. 2020 Medium

    A series of post-translational regulators (DNMT1 stabilization, parkin/STUB1 degradation) and a synthetic feedforward DNA-methylation loop expanded the network controlling ERRα abundance and activity.

    Evidence Protein stability and ubiquitination assays, bisulfite sequencing, and co-IP across breast cancer and endothelial models

    PMID:30244249 PMID:31907393 PMID:32855526

    Open questions at the time
    • Hierarchy among competing E3 ligases and stabilizers unresolved
    • Mostly single-lab pharmacological studies
  20. 2022 High

    Genetic dissection of the insulin/GSK3β/FBXW7 axis and the RBBP6 ligase established degradation-controlled ERRα as a sensor coupling hormonal and disease states to metabolic output.

    Evidence Liver-specific GSK3β/FBXW7 knockouts, ERRα phosphosite knock-in mice, and K100 ubiquitination mutagenesis in diabetic kidney models

    PMID:35440636 PMID:39441040

    Open questions at the time
    • Integration of multiple ligase inputs on a shared ERRα pool not modeled
  21. 2024 High

    Adipocyte-specific deletion and the mevalonate-senescence axis showed ERRα coordinates bone marrow stromal fate and sterol-driven cellular senescence in vivo.

    Evidence Adipocyte-specific ESRRA knockout, leptin promoter ChIP, OVX/obesity models, and high-fat-diet senescence assays in knockouts

    PMID:38216569 PMID:38704393

    Open questions at the time
    • Cell-type specificity of cholesterol/mevalonate effects not fully separated

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how ERRα's competing degradation/stabilization inputs, its sterol-ligand sensing, and its transcription-independent functions are integrated to set context-specific output in vivo.
  • No unified model reconciling the multiple E3 ligases and stabilizers
  • Structural basis of cholesterol agonism in the occluded pocket undefined
  • Switch between transcriptional and non-transcriptional modes uncharacterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003677 DNA binding 6 GO:0140110 transcription regulator activity 6 GO:0008289 lipid binding 2 GO:0098772 molecular function regulator activity 2
Localization
GO:0005634 nucleus 4 GO:0005829 cytosol 1
Pathway
R-HSA-1430728 Metabolism 6 R-HSA-392499 Metabolism of proteins 4 R-HSA-1643685 Disease 3 R-HSA-1852241 Organelle biogenesis and maintenance 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-9612973 Autophagy 3 R-HSA-168256 Immune System 2 R-HSA-9909396 Circadian clock 1
Partners
HDAC4IRF3KDM1APERM1PPARGC1APPARGC1BSIRT1TBK1
Complex memberships
PGC-1α/ERRα transcriptional complex

Evidence

Reading pass · 51 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2004 Crystal structure of ERRα ligand-binding domain (LBD) complexed with a PGC-1α coactivator peptide reveals a transcriptionally active conformation in the absence of a ligand. The putative ligand-binding pocket is almost completely occupied by bulky side chains (particularly Phe328), providing structural evidence for ligand-independent transcriptional activation. The structure also reveals how a PGC-1α LLXYL (inverted LXXLL) motif binds the LBD. X-ray crystallography at 2.5 Å resolution; binding affinity assays with PGC-1α peptides The Journal of biological chemistry High 15337744
2004 ERRα is a downstream effector of PGC-1α in mitochondrial biogenesis: inhibition of ERRα compromises PGC-1α-induced expression of mitochondrial protein-encoding genes and mitochondrial DNA content. A constitutively active ERRα is sufficient to induce both responses. ERRα binding sites in promoters of target genes contribute to the PGC-1α transcriptional response. Dominant-negative and constitutively active ERRα overexpression; mitochondrial DNA quantification; reporter/promoter assays Proceedings of the National Academy of Sciences of the United States of America High 15087503
2004 ERRα autoregulates its own expression via a polymorphic 23-bp hormone response element (ESRRA23) in the human ESRRA promoter that binds ERRα. PGC-1α induces ESRRA promoter activity in an ESRRA23- and ERRα-dependent manner, and co-expression of ERRα and PGC-1α synergistically activates the promoter. Chromatin immunoprecipitation confirmed endogenous ERRα occupies its own promoter in vivo. ChIP; luciferase reporter assays; ERRα null fibroblasts; transient transfection The Journal of biological chemistry High 14978033
2004 ERRα directly regulates the apolipoprotein A-IV (apoA-IV) promoter via interaction with the apoC-III enhancer element; ERRα cooperates with PGC-1α to activate apoA-IV transcription. ERRα knockout mice display lipid malabsorption and reduced enterocyte β-oxidation capacity, establishing ERRα as a direct transcriptional regulator of intestinal lipid handling. Microarray; promoter luciferase assays; ERRα knockout mice; isolated enterocyte β-oxidation assays The Journal of biological chemistry High 15466464
2005 PGC-1α drives mitofusin 2 (Mfn2) gene expression through ERRα in an ERRα-dependent transcriptional programme, linking the PGC-1α/ERRα axis to mitochondrial fusion and architecture in skeletal muscle. In vitro cellular reporter assays; mRNA expression analysis in human exercise cohort The Journal of physiology Medium 15961417
2005 ERRα controls morphogenetic movements (epiboly and convergent-extension) during zebrafish gastrulation. Loss-of-function via morpholinos or dominant-negative ERRα disrupts these movements; gain-of-function by mRNA injection also perturbs them, establishing a role in early embryonic development independent of cell fate determination. Zebrafish morpholino knockdown; dominant-negative overexpression; mRNA injection gain-of-function Developmental biology Medium 15848392
2007 ERRα is required for the bioenergetic adaptation to cardiac pressure overload: ERRα−/− mice develop heart failure with abnormal phosphocreatine depletion and reduced maximal mitochondrial ATP synthesis rates. ERRα target genes involved in energy substrate oxidation, ATP synthesis, and phosphate transfer are downregulated at baseline or with pressure overload. ERRα knockout mice; left ventricular pressure overload model; 31P-NMR; mitochondrial respiration assays; gene expression analysis Cell metabolism High 17618854
2010 ERRα and PGC-1β co-occupy the ERBB2 amplicon on chromosome 17q12-21 in human breast cancer cells, directing co-recruitment of PGC-1β and RNA polymerase II to ERBB2 and co-amplified gene promoters. ERRα ablation delays ERBB2-induced mammary tumor development and lowers amplicon transcript levels. ERRα also competitively displaces ERα from the ERBB2 locus to de-repress expression. Chromosome 17q-wide ChIP; ERRα knockout mouse mammary tumor model; RNA polymerase II ChIP; tamoxifen sensitivity assays Cancer research High 20961995
2011 ERRα directly regulates all major molecular clock components and is an output gene of the circadian oscillator (shown by Clock/Clock mutant mice). Genome-wide ChIP-seq identified extensive overlap between ERRα, its corepressor PROX1, and the core clock factor BMAL1 binding sites in liver, establishing transcriptional regulatory loops between these factors controlling daily metabolic rhythms. ERRα-null mice display deregulated locomotor activity rhythms and time-dependent hypoglycemia/hypoinsulinemia. ChIP-seq; ERRα-null mouse phenotyping; Clock mutant mice; circadian locomotor activity analysis; metabolic profiling PLoS genetics High 21731503
2011 A recurrent ESRRA-C11orf20 fusion transcript, joining 5′ exons of ESRRA to 3′ exons of C11orf20, was identified in ~15% of serous ovarian carcinomas by deep paired-end mRNA sequencing, with a corresponding genomic rearrangement confirmed in tumor samples. Deep paired-end RNA sequencing; RT-PCR validation; targeted genomic resequencing PLoS biology Medium 21949640
2012 ERRα directly binds an evolutionarily conserved response element in the PGC-1α promoter and is required for PGC-1α expression in primary cardiomyocytes. Overexpression of ERRα overcomes HDAC5-mediated repression of PGC-1α. Hypoxia reduces ERRα mRNA, preceding loss of PGC-1α mRNA, though ChIP shows ERRα loss is not responsible for PGC-1α loss during hypoxia. Luciferase reporter assays; ERRα overexpression/knockdown in primary cardiomyocytes; ChIP; HDAC5 co-expression Biochemistry and cell biology Medium 23668787
2013 mTOR occupies regulatory regions of ERRα target genes (TCA cycle, lipid biosynthesis) genome-wide in mouse liver. mTOR regulates ERRα activity through ubiquitin-mediated proteasomal degradation via transcriptional control of the ubiquitin-proteasome pathway. Combined genetic/pharmacological inhibition of ERRα and rapamycin exacerbates hepatic hyperlipidemia, placing ERRα downstream of mTOR in hepatic lipid metabolism. ChIP-seq in mouse liver; genetic ERRα ablation; rapamycin treatment; TCA metabolite quantification; hepatic lipid measurement Cell metabolism High 23562079
2013 ERRα regulates colon cancer cell proliferation, colony formation, and tumorigenic capacity. ERRα depletion causes G1-to-S cell cycle arrest with reduced CDK2 activity and altered retinoblastoma phosphorylation. ERRα-depleted cells show reduced expression of glycolysis, TCA cycle, and lipid synthesis genes, and reduced glucose incorporation and glucose-mediated lipogenesis measured by 14C isotope tracing. shRNA knockdown; colony formation assays; xenograft; cell cycle analysis; 14C isotope tracer analysis Carcinogenesis Medium 23720198
2013 ESRRA and HDAC4 interact both in vitro (HeLa cells) and in vivo (mouse cortex). HDAC4 potently represses ESRRA-induced target gene expression. A missense mutation in ESRRA decreases its transcriptional activity, while an HDAC4 mutation increases repression of ESRRA target genes, establishing a functional ESRRA-HDAC4 transcriptional regulatory axis. Co-immunoprecipitation in HeLa cells and mouse cortex; transcriptional activity assays; whole-genome/exome sequencing of human families The Journal of clinical investigation Medium 24216484
2015 ERRα and ERRγ together are required for cardiomyocyte metabolism and cardiac function: mice lacking both ERRα and cardiac ERRγ develop severe bradycardia, lethal cardiomyopathy, and heart failure. ERRα and ERRγ directly control genes for mitochondrial function/dynamics and genes for contraction, calcium homeostasis, and conduction. ERRα/ERRγ double-knockout mice; cardiac phenotyping; transcriptional target gene analysis Molecular and cellular biology High 25624346
2015 ERRα negatively regulates TLR-induced inflammation in macrophages by directly binding the Tnfaip3 (A20 deubiquitinase) promoter to promote its transcription. ERRα also regulates NF-κB signaling by controlling p65 acetylation via maintenance of NAD+ levels and sirtuin 1 activation. ERRα-deficient macrophages display increased glycolysis and impaired mitochondrial respiratory function. ERRα knockout mice; ChIP; promoter assays; NF-κB p65 acetylation measurement; NAD+ quantification; Seahorse metabolic flux analysis Immunity High 26200012
2015 ERRα directly binds the Sirt3 promoter as its transcription factor (in a PGC-1α/ERRα complex) to regulate Sirt3 expression and dopaminergic neuronal survival. PGC-1α interacts with ERRα for this function. Loss of the PGC-1α/ERRα-Sirt3 pathway leads to elevated acetylation of SOD2 (K130) and ATP synthase β (K485) and dopaminergic neuronal death. ChIP; co-immunoprecipitation; promoter reporter assays; MPTP mouse model; Sirt3 knockout mice Antioxidants & redox signaling Medium 26421366
2016 Cholesterol was identified as an endogenous ERRα agonist by affinity chromatography of tissue lipidomes with the ERRα LBD followed by transcriptional assays. In bone, cholesterol effects, statin effects, and bisphosphonate osteoprotection on osteoclastogenesis all require ERRα; these effects are lost in ERRα knockout mice. Affinity chromatography; transcriptional activation assays; ERRα knockout mice; osteoclastogenesis assays; in vivo bone loss models Cell metabolism High 26777690
2016 Lapatinib induces degradation of ERRα protein. In lapatinib-resistant breast cancer cells, mTOR reactivation restores ERRα expression, which triggers metabolic adaptations including increased glutamine metabolism and ROS detoxification. An ERRα inverse agonist counteracts these metabolic adaptations and overcomes lapatinib resistance in a HER2-induced mouse mammary tumor model. Protein stability assays; mTOR inhibition; metabolic flux analysis (glutamine); ROS measurement; ERRα inverse agonist treatment; HER2 mouse tumor model Nature communications High 27402251
2016 The PGC-1α/ERRα axis negatively regulates one-carbon metabolism genes, reducing purine biosynthesis in breast cancer cells. Activation of AMPK increases PGC-1α/ERRα expression and ERRα binding to target sites. This repression of the folate cycle by ERRα promotes sensitivity to the anti-folate drug methotrexate in vitro and in vivo. ChIP-seq; gene-expression datasets; AMPK activation; ERRα binding site analysis; methotrexate sensitivity assays in mice Cell reports Medium 26804918
2016 MYC drives metabolic reprogramming to an oxidative state during osteoclast differentiation and transcriptionally induces ERRα. ERRα then cooperates with NFATc1 to drive osteoclastogenesis. Pharmacological inhibition of ERRα attenuated ovariectomy-induced bone loss in mice. Osteoclast-specific Myc deletion increased bone mass and protected against OVX-induced osteoporosis. Osteoclast-specific Myc knockout mice; transcriptomic analysis; pharmacological ERRα inhibition; OVX mouse model The Journal of clinical investigation High 28530645
2016 ERRα induces LSD1 to demethylate H3K9 (rather than its default H3K4 substrate) at the transcriptional start site of commonly activated target genes including MMP1. ERRα is sufficient to switch LSD1 substrate specificity to H3K9 demethylation in vitro. This ERRα-LSD1 axis promotes cell invasion, which is rescued by MMP1 re-expression after LSD1 or ERRα depletion. In vitro H3K9 demethylation assay with purified ERRα and LSD1; ChIP for H3K9me marks; siRNA depletion; invasion assays; MMP1 rescue Proceedings of the National Academy of Sciences of the United States of America High 28348226
2017 ESRRA is required for autophagosome formation and autophagy-mediated antimicrobial defense against mycobacterial infection. AMPK pathway and SIRT1 activation induce ESRRA, which transcriptionally activates Atg genes via ERR response elements. Additionally, ESRRA operates in a feed-forward loop with SIRT1 to deacetylate ATG5, BECN1, and ATG7, activating autophagy post-translationally. ESRRA knockout macrophages; ChIP/promoter analysis of Atg genes; SIRT1 deacetylation assays; mycobacterial infection assays; autophagy flux measurement Autophagy High 28841353
2017 ERRα negatively regulates type I interferon (IFN-I) production by associating with TBK1 and IRF3 to impede TBK1-IRF3 complex formation, IRF3 phosphorylation, IRF3 dimerization, and DNA binding. Viral infection induces TBK1-dependent ERRα stabilization. This anti-viral regulatory function is independent of ERRα transcriptional activity and PGC-1α. ERRα knockout mice; co-immunoprecipitation of TBK1-ERRα-IRF3 complex; IRF3 phosphorylation and dimerization assays; DNA binding assays; viral infection models PLoS pathogens High 28591144
2017 LSD1 protects ERRα from ubiquitination and proteasomal degradation independently of LSD1's demethylase activities, resulting in elevated ERRα protein levels in breast cancer cells. Ubiquitination assays; LSD1 demethylase-inactive mutants; co-immunoprecipitation; ERRα protein stability measurement PloS one Medium 29190800
2017 ERRα directly transactivates the TMPRSS2:ERG fusion gene in prostate cancer cells via both ERR-binding element- and AR-binding element-dependent mechanisms. ERG expressed by the T:E fusion in turn transactivates the ESRRA gene, forming a reciprocal ERRα-ERG regulatory loop that promotes advanced prostate cancer growth. Luciferase reporter assays; ChIP; ERRα inverse agonist treatment; ERRα/ERG overexpression; in vivo metastasis assays Oncogene Medium 30042415
2018 Thyroid hormone (TH) increases ESRRA expression and activity through THRB1-dependent induction of PGC1α. ESRRA mediates TH-induced mitochondrial biogenesis, fission, and mitophagy. Mechanistically, ESRRA induces ULK1 expression, which then promotes DRP1-mediated fission and activates FUNDC1-MAP1LC3B-II interaction to induce mitophagy. siRNA knockdown of ESRRA, ULK1, DRP1, or FUNDC1 inhibits TH-induced mitophagy and decreases OXPHOS. Transcriptome analysis; ChIP-seq; siRNA knockdown; mitochondrial biogenesis/fission/mitophagy functional assays; co-immunoprecipitation (FUNDC1-LC3) Science signaling High 29945885
2018 ERRα promotes breast cancer cell dissemination to bone by directly transactivating the RANK gene. ChIP and bioinformatics confirmed RANK as an ERRα target. ERRα overexpression promotes spontaneous bone micro-metastases in vivo; pharmacological ERRα inhibition reduces bone metastases and RANK expression. ChIP; transactivation assays; in vivo orthotopic breast cancer model; pharmacological ERRα inhibition; meta-analysis of human cohorts Oncogene Medium 30478447
2018 PERM1 physically interacts with ERRα in cardiomyocytes and the mouse heart (co-immunoprecipitation). PERM1 is recruited to ERR target gene promoters and activates their transcription partially through ERRα. Mammalian one-hybrid assay showed PERM1 activates transcription when recruited to a promoter, blunted by silencing PGC-1α, BAG6, or KANK2. PERM1 knockout mice show reduced cardiac function and energy reserves. Co-immunoprecipitation; DNA binding assays; reporter gene assays; Perm1 knockout mice; echocardiography; proteomics/metabolomics Frontiers in cardiovascular medicine Medium 36419485
2018 ERRα directly activates androgen response element (ARE)-containing promoters such as the PSA promoter in prostate cells, independent of androgen receptor expression or activity. All ERR subfamily members can activate steroid response element-containing promoters even in the presence of antisteroid compounds. ERRα inverse agonist treatment; ARE-containing promoter reporter assays; androgen receptor expression analysis Nucleic acids research Medium 18697814
2020 In kidney proximal tubule cells, ESRRA directly controls both metabolic (fatty acid oxidation, oxidative phosphorylation) and proximal tubule cell-specific differentiation genes. ERRα knockout in mouse models of kidney disease worsens PT cell differentiation defects and disease, establishing that ERRα couples metabolism and differentiation in PT cells. scRNA-seq; cell trajectory analyses; ERRα knockout mouse models; ChIP/transcriptional target analysis in mouse and patient samples Cell metabolism High 33301705
2020 ESRRA activates autophagic flux and controls gut microbiota composition to maintain intestinal homeostasis. esrra-null mice show depressed AMPK phosphorylation, lower TFEB levels, and accumulation of p62 with defective mitochondria. Fecal microbiota transplantation from WT mice ameliorated colitis severity in Esrra-deficient mice. Esrra knockout mice; DSS colitis model; autophagy flux assays; gut microbiota analysis; fecal microbiota transplantation Autophagy Medium 33172329
2020 DNMT1 promotes ERRα protein stability; ERRα in turn couples DNMT1 transcription with that of the methionine cycle and S-adenosylmethionine synthesis, driving DNA methylation. Combined inhibition of ERRα and DNMT1 (5-azadC) reverses IRF4 promoter hypermethylation and de-represses this tumor suppressor gene to suppress breast cancer in vivo. Genetic/pharmacological manipulation; bisulfite genomic sequencing; pre-clinical mouse model of breast cancer; protein stability assays; methylation analysis Oncogene Medium 32855526
2020 ERRα directly transactivates two key steroidogenic enzyme genes, CYP11A1 and AKR1C3, to promote intratumoral androgen (DHT) biosynthesis in castration-resistant prostate cancer. ERRα inverse agonist reduces DHT production and suppresses AR signaling in prostate cancer cells. ERRα overexpression/knockdown; UPLC-MS/MS intratumoral androgen measurement; ERRα inverse agonist treatment; ChIP/promoter transactivation assays Theranostics Medium 32226548
2020 ESRRA acts as a key regulator of intestinal homeostasis; ERRα-deficient mice were more susceptible to DSS-induced colitis, with impaired intestinal epithelial cell compensatory proliferation, enhanced apoptosis, and reduced goblet cell counts. ERRα exerts protective effects within the radio-resistant compartment via transcriptional control of intestinal homeostasis genes. ERRα knockout mice; DSS colitis model; microbiota analysis; epithelial proliferation/apoptosis assays; bone marrow transplantation Scientific reports Medium 34302001
2022 Insulin enhances ERRα activity via a GSK3β/FBXW7 signaling axis: insulin inhibits GSK3β, preventing FBXW7-mediated ubiquitination and proteasomal degradation of ERRα, thus stabilizing ERRα. Liver-specific deletion of GSK3β or FBXW7 and ERRα phosphosite mutant (ERRα3SA) mice accumulate ERRα protein that no longer responds to fluctuating insulin levels, resulting in compromised energy homeostasis and reduced insulin sensitivity. Liver-specific conditional knockout mice (GSK3β, FBXW7); ERRα phosphosite knock-in mice (ERRα3SA); transcriptome analysis; insulin sensitivity assays; protein stability/ubiquitination assays Nature communications High 35440636
2022 RBBP6 E3 ubiquitin ligase promotes ERRα degradation through K48-linked polyubiquitination at the K100 residue of ERRα. This RBBP6-mediated ERRα degradation contributes to mitochondrial injury in proximal tubule cells in diabetic kidney disease. Conditional ERRα overexpression or RBBP6 inhibition reduced mitochondrial damage in diabetic mice. Biochemical ubiquitination assays; site-directed mutagenesis (K100); co-immunoprecipitation; conditional ERRα overexpression in DKD mouse models; human DKD specimens Advanced science High 39441040
2020 Carnosic acid directly binds the ligand-binding domain of ERRα and promotes ERRα ubiquitination and proteasomal degradation. STUB1 was identified as the E3 ligase of ERRα. Lysine residues K51 and K68 are essential for ERRα ubiquitination and degradation. Carnosic acid also decreases the interaction between ERRα and PGC1β. Direct LBD binding assay; ubiquitination assay with STUB1; site-directed mutagenesis (K51, K68); co-immunoprecipitation ERRα-PGC1β; osteoclastogenesis and OVX mouse model Cell death and differentiation Medium 31907393
2021 ERRα directly binds the DSN1 promoter (confirmed by ChIP and dual-luciferase assays) to transcriptionally activate DSN1, which then promotes cell cycle progression via the CDC25C/CDK1/CyclinB1 pathway. ERRα silencing causes G2M arrest in gastric cancer cells via this pathway. RNA-seq; dual-luciferase reporter assay; ChIP; flow cytometry; ERRα silencing International journal of biological sciences Medium 34131395
2021 FBXL10 interacts with ERRα (identified by mass spectrometry), stabilizes ERRα protein by reducing poly-ubiquitylation and promoting mono-ubiquitylation, increases ERRα transcriptional activity and promoter occupancy, and facilitates ERRα/PGC1β-mediated breast cancer cell proliferation and tumorigenesis in vitro and in vivo. Mass spectrometry interaction screen; co-immunoprecipitation; ubiquitination assays; reporter gene assay; ChIP; xenograft mouse model Cancer letters Medium 33450359
2022 Cholesterol accumulation in lipid rafts during EGFR-TKI resistance promotes EGFR-Src interaction and EGFR/Src/Erk signaling reactivation, leading to SP1 nuclear translocation and SP1-dependent transcriptional upregulation of ERRα. ERRα re-expression sustains ROS detoxification in resistant cells. SP1 binding to the ERRα promoter was confirmed by luciferase reporter and ChIP assays. Co-immunoprecipitation; luciferase reporter assay; ChIP; immunofluorescence; xenograft mouse model Molecular cancer Medium 35303882
2022 ERRα binds to the NLRP3 promoter (confirmed by CUT&Tag) and inhibits caspase-1/GSDMD signaling to reduce pyroptosis in endometrial cancer. ERRα also activates glycolytic rate-limiting enzymes and bridges glycolytic metabolism with pyroptosis resistance. ERRα-HIF-1α interaction was confirmed by co-immunoprecipitation. Co-immunoprecipitation (ERRα-HIF-1α); dual-luciferase reporter; CUT&Tag sequencing; flow cytometry; electron microscopy; organoid and xenograft models Journal of experimental & clinical cancer research Medium 37864196
2023 SLU-PP-332, a synthetic pan-ERR agonist with highest potency for ERRα, increases mitochondrial function and cellular respiration in skeletal muscle cells, increases type IIa oxidative muscle fibers, and enhances exercise endurance in mice. SLU-PP-332 induces an ERRα-specific acute aerobic exercise genetic program; ERRα activation is critical for enhanced exercise endurance. ERR agonist pharmacological characterization; ERRα-specific genetic models; Seahorse metabolic flux; skeletal muscle fiber typing; mouse exercise endurance testing ACS chemical biology Medium 36988910
2024 Adipocyte-specific ESRRA deficiency preserves osteogenesis and vascular formation in adipocyte-rich bone marrow under estrogen deficiency or obesity. Mechanistically, adipocyte ESRRA suppresses SPP1 transcription (by interfering with E2/ESR1 signaling) and positively drives leptin expression by directly binding the leptin promoter. ESRRA abrogation enhances SPP1 secretion and decreases leptin, coordinately dictating bone marrow stromal stem cell fate and restoring type H vessel formation. Adipocyte-specific ESRRA knockout mice; OVX and obesity models; ChIP (leptin promoter); pharmacological ERRα inhibition; SPP1 and leptin secretion assays Nature communications High 38704393
2024 The cholesterol/mevalonate biosynthetic pathway promotes ERRα transcriptional activity, leading to dysfunctional mitochondria, ROS production, DNA damage, and p53-dependent cellular senescence. This mevalonate-induced senescence is abrogated in ERRα knockout mice on a high-fat diet in vivo. ERRα knockout mice; high-fat diet model; mevalonate pathway inhibition; ROS and mitochondrial function assays; p53 pathway analysis npj aging Medium 38216569
2025 IL-6 suppresses mitochondrial function via a JAK1/STAT1/3 axis that upregulates HIF1A and ERRα transcription. ERRα then stabilizes HIF1α protein, which in turn inhibits ERRα—establishing a negative feedback loop. This IL-6-mediated suppression operates when PGC1 expression is low; higher PGC1 rescues ERRα from HIF1α-mediated inhibition to restore mitochondrial respiration. JAK1 inhibitors; STAT1/3 pathway analysis; ERRα transcription/protein stability assays; HIF1α stabilization assays; PGC1 overexpression rescue; Seahorse metabolic flux Cell reports Medium 40056415
2016 ERRα negatively regulates S6K1 expression by directly binding to the S6K1 promoter. Downregulation of ERRα sensitizes ERα-negative breast cancer cells to mTORC1/S6K1 inhibitors. ChIP (ERRα at S6K1 promoter); ERRα knockdown; mTORC1/S6K1 inhibitor sensitivity assays Signal transduction and targeted therapy Medium 28890840
2019 The PGC1α-ERRα transcriptional complex suppresses prostate cancer invasion by downregulating MYC and inhibiting integrin alpha1 and beta4 expression. CRISPR/Cas9 deletion of ERRα abolishes PGC1α regulation of cytoskeletal organization and invasiveness. PGC1α and ERRα associate at the MYC promoter (confirmed by ChIP), supporting their inhibitory activity on MYC transcription. CRISPR/Cas9 ERRα deletion; PGC1α overexpression; ChIP (PGC1α/ERRα at MYC promoter); invasion assays in vitro and in vivo; integrin expression analysis Cancer research Medium 31594836
2017 Parkin overexpression promotes ERRα ubiquitination and degradation, reducing ERRα protein levels and consequently decreasing eNOS (total and phosphorylated) in endothelial cells. ERRα overexpression increases eNOS levels; this parkin-eNOS regulatory effect is independent of autophagy and apoptosis. Parkin plasmid overexpression; co-immunoprecipitation; ERRα ubiquitination assay; flow cytometry; ERRα inhibitor treatment; siRNA knockdown Cellular physiology and biochemistry Medium 30244249
2016 PGC-1α and PGC-1β increase creatine transporter (CrT/Slc6a8) expression and creatine uptake in myotubes via ERRα. An ERR response element (ERRE) was identified in the CrT gene first intron and upstream promoter. ChIP assays confirmed that PGC-1α and ERRα directly interact with the CrT gene. shRNA knockdown of ERRα inhibited the PGC-1-mediated increase in CrT expression. ChIP (ERRα at CrT gene); adenoviral overexpression; shRNA knockdown; creatine uptake assay; constitutively active ERRα (VP16-ERRα) Biochimica et biophysica acta Medium 25173818
1997 The human ESRL1 (ERRα) gene is localized to chromosome 11q12 by FISH, consists of 7 exons spanning ~20 kb, and has a GC-rich promoter with 10 Sp1 sites and two E-boxes but no TATA or CAAT boxes. Multiple transcription initiation start sites were identified. ERRα modulates estrogen responsiveness of the lactoferrin gene promoter in endometrial carcinoma cells. FISH; gene cloning and sequencing; primer extension; RNase protection assay; transient transfection reporter assay Genomics Medium 9286700

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2004 The estrogen-related receptor alpha (ERRalpha) functions in PPARgamma coactivator 1alpha (PGC-1alpha)-induced mitochondrial biogenesis. Proceedings of the National Academy of Sciences of the United States of America 560 15087503
2005 Mitofusins 1/2 and ERRalpha expression are increased in human skeletal muscle after physical exercise. The Journal of physiology 334 15961417
2007 The nuclear receptor ERRalpha is required for the bioenergetic and functional adaptation to cardiac pressure overload. Cell metabolism 224 17618854
2008 ERRalpha: a metabolic function for the oldest orphan. Trends in endocrinology and metabolism: TEM 215 18778951
2008 PGC-1alpha and ERRalpha target gene downregulation is a signature of the failing human heart. Journal of molecular and cellular cardiology 185 19061896
2004 Evidence for ligand-independent transcriptional activation of the human estrogen-related receptor alpha (ERRalpha): crystal structure of ERRalpha ligand binding domain in complex with peroxisome proliferator-activated receptor coactivator-1alpha. The Journal of biological chemistry 185 15337744
2020 The Nuclear Receptor ESRRA Protects from Kidney Disease by Coupling Metabolism and Differentiation. Cell metabolism 151 33301705
2004 A polymorphic autoregulatory hormone response element in the human estrogen-related receptor alpha (ERRalpha) promoter dictates peroxisome proliferator-activated receptor gamma coactivator-1alpha control of ERRalpha expression. The Journal of biological chemistry 142 14978033
2016 Ligand Activation of ERRα by Cholesterol Mediates Statin and Bisphosphonate Effects. Cell metabolism 130 26777690
2022 Cholesterol promotes EGFR-TKIs resistance in NSCLC by inducing EGFR/Src/Erk/SP1 signaling-mediated ERRα re-expression. Molecular cancer 129 35303882
2013 Molecular and genetic crosstalks between mTOR and ERRα are key determinants of rapamycin-induced nonalcoholic fatty liver. Cell metabolism 128 23562079
2018 Thyroid hormone receptor and ERRα coordinately regulate mitochondrial fission, mitophagy, biogenesis, and function. Science signaling 116 29945885
2015 Orphan Nuclear Receptor ERRα Controls Macrophage Metabolic Signaling and A20 Expression to Negatively Regulate TLR-Induced Inflammation. Immunity 116 26200012
2015 PGC-1α/ERRα-Sirt3 Pathway Regulates DAergic Neuronal Death by Directly Deacetylating SOD2 and ATP Synthase β. Antioxidants & redox signaling 114 26421366
2015 Estrogen-related receptor α (ERRα) and ERRγ are essential coordinators of cardiac metabolism and function. Molecular and cellular biology 113 25624346
2017 MYC-dependent oxidative metabolism regulates osteoclastogenesis via nuclear receptor ERRα. The Journal of clinical investigation 102 28530645
2016 ERRα mediates metabolic adaptations driving lapatinib resistance in breast cancer. Nature communications 96 27402251
2004 Estrogen-related receptor alpha (ERRalpha) is a transcriptional regulator of apolipoprotein A-IV and controls lipid handling in the intestine. The Journal of biological chemistry 95 15466464
2023 Genistein mitigates senescence of bone marrow mesenchymal stem cells via ERRα-mediated mitochondrial biogenesis and mitophagy in ovariectomized rats. Redox biology 93 36871183
1997 Expression of the estrogen-related receptor 1 (ERR-1) orphan receptor during mouse development. Mechanisms of development 89 9256346
2011 Genomic convergence among ERRα, PROX1, and BMAL1 in the control of metabolic clock outputs. PLoS genetics 84 21731503
2019 ERRα as a Bridge Between Transcription and Function: Role in Liver Metabolism and Disease. Frontiers in endocrinology 83 31024446
2004 Effects of estradiol, benzophenone-2 and benzophenone-3 on the expression pattern of the estrogen receptors (ER) alpha and beta, the estrogen receptor-related receptor 1 (ERR1) and the aryl hydrocarbon receptor (AhR) in adult ovariectomized rats. Toxicology 80 15458797
2016 The PGC-1α/ERRα Axis Represses One-Carbon Metabolism and Promotes Sensitivity to Anti-folate Therapy in Breast Cancer. Cell reports 79 26804918
2017 ERRα induces H3K9 demethylation by LSD1 to promote cell invasion. Proceedings of the National Academy of Sciences of the United States of America 75 28348226
2010 Transcriptional control of the ERBB2 amplicon by ERRalpha and PGC-1beta promotes mammary gland tumorigenesis. Cancer research 74 20961995
2017 ESRRA (estrogen-related receptor α) is a key coordinator of transcriptional and post-translational activation of autophagy to promote innate host defense. Autophagy 73 28841353
2020 ESRRA (estrogen related receptor alpha) is a critical regulator of intestinal homeostasis through activation of autophagic flux via gut microbiota. Autophagy 68 33172329
2013 Estrogen-related receptor-α (ERRα) deficiency in skeletal muscle impairs regeneration in response to injury. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 66 24277576
2013 Eating disorder predisposition is associated with ESRRA and HDAC4 mutations. The Journal of clinical investigation 65 24216484
2016 Aging Reduces an ERRalpha-Directed Mitochondrial Glutaminase Expression Suppressing Glutamine Anaplerosis and Osteogenic Differentiation of Mesenchymal Stem Cells. Stem cells (Dayton, Ohio) 59 27501743
2023 ERRα promotes glycolytic metabolism and targets the NLRP3/caspase-1/GSDMD pathway to regulate pyroptosis in endometrial cancer. Journal of experimental & clinical cancer research : CR 57 37864196
2020 Cholesterol and Mevalonate: Two Metabolites Involved in Breast Cancer Progression and Drug Resistance through the ERRα Pathway. Cells 56 32751976
2019 PGC1α Suppresses Prostate Cancer Cell Invasion through ERRα Transcriptional Control. Cancer research 56 31594836
2019 Dynamic transcriptomic analysis reveals suppression of PGC1α/ERRα drives perturbed myogenesis in facioscapulohumeral muscular dystrophy. Human molecular genetics 55 30462217
2015 ERRα Is a Marker of Tamoxifen Response and Survival in Triple-Negative Breast Cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 51 26542058
2004 Expression of the orphan nuclear receptor ERRalpha is under circadian regulation in estrogen-responsive tissues. Journal of molecular endocrinology 49 15291745
2020 Dual targeting of SREBP2 and ERRα by carnosic acid suppresses RANKL-mediated osteoclastogenesis and prevents ovariectomy-induced bone loss. Cell death and differentiation 47 31907393
2013 ERRα metabolic nuclear receptor controls growth of colon cancer cells. Carcinogenesis 47 23720198
2022 Lipid reprogramming induced by the TFEB-ERRα axis enhanced membrane fluidity to promote EC progression. Journal of experimental & clinical cancer research : CR 45 35045880
2020 A novel miR-1291-ERRα-CPT1C axis modulates tumor cell proliferation, metabolism and tumorigenesis. Theranostics 45 32641987
2015 Estrogen related receptor α (ERRα) a promising target for the therapy of adrenocortical carcinoma (ACC). Oncotarget 45 26312764
2009 Estrogen-related receptor alpha (ERRalpha) inverse agonist XCT-790 induces cell death in chemotherapeutic resistant cancer cells. Chemico-biological interactions 44 19464277
2021 ESRRA promotes gastric cancer development by regulating the CDC25C/CDK1/CyclinB1 pathway via DSN1. International journal of biological sciences 43 34131395
2018 Cholesterol as an Endogenous ERRα Agonist: A New Perspective to Cancer Treatment. Frontiers in endocrinology 43 30254608
2011 ESRRA-C11orf20 is a recurrent gene fusion in serous ovarian carcinoma. PLoS biology 43 21949640
2018 Nuclear receptor ERRα and transcription factor ERG form a reciprocal loop in the regulation of TMPRSS2:ERG fusion gene in prostate cancer. Oncogene 42 30042415
2021 Triple-negative breast lobular carcinoma: a luminal androgen receptor carcinoma with specific ESRRA mutations. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 40 33753865
2008 Estrogen receptor-related receptor alpha (ERRalpha) regulates osteopontin expression through a non-canonical ERRalpha response element in a cell context-dependent manner. Journal of molecular endocrinology 40 18234909
2016 miR-135a Inhibits the Invasion of Cancer Cells via Suppression of ERRα. PloS one 39 27227989
2016 Curcumin Promotes Osteosarcoma Cell Death by Activating miR-125a/ERRα Signal Pathway. Journal of cellular biochemistry 39 27231954
2015 Reprogramming of the ERRα and ERα target gene landscape triggers tamoxifen resistance in breast cancer. Cancer research 39 25643697
2020 Inhibition of DNMT1 and ERRα crosstalk suppresses breast cancer via derepression of IRF4. Oncogene 38 32855526
2017 ERRα regulates the growth of triple-negative breast cancer cells via S6K1-dependent mechanism. Signal transduction and targeted therapy 38 28890840
2023 Synthetic ERRα/β/γ Agonist Induces an ERRα-Dependent Acute Aerobic Exercise Response and Enhances Exercise Capacity. ACS chemical biology 36 36988910
2014 miR-125a inhibits porcine preadipocytes differentiation by targeting ERRα. Molecular and cellular biochemistry 35 24952481
1997 Human estrogen receptor-like 1 (ESRL1) gene: genomic organization, chromosomal localization, and promoter characterization. Genomics 34 9286700
2018 ERRα promotes breast cancer cell dissemination to bone by increasing RANK expression in primary breast tumors. Oncogene 33 30478447
2008 The orphan receptor ERRalpha interferes with steroid signaling. Nucleic acids research 32 18697814
2019 ERR1 and PGC1α associated mitochondrial alterations correlate with pan-cancer disparity in African Americans. The Journal of clinical investigation 30 30920960
2017 ERRα Maintains Mitochondrial Oxidative Metabolism and Constitutes an Actionable Target in PGC1α-Elevated Melanomas. Molecular cancer research : MCR 29 28596418
1997 Chromosomal mapping of the human and murine orphan receptors ERRalpha (ESRRA) and ERRbeta (ESRRB) and identification of a novel human ERRalpha-related pseudogene. Genomics 28 9344655
2024 Targeting adipocyte ESRRA promotes osteogenesis and vascular formation in adipocyte-rich bone marrow. Nature communications 27 38704393
2020 Nuclear receptor ERRα contributes to castration-resistant growth of prostate cancer via its regulation of intratumoral androgen biosynthesis. Theranostics 27 32226548
2018 PGC-1α and PGC-1β Increase Protein Synthesis via ERRα in C2C12 Myotubes. Frontiers in physiology 27 30356878
2018 ERRα suppression enhances the cytotoxicity of the MEK inhibitor trametinib against colon cancer cells. Journal of experimental & clinical cancer research : CR 26 30185207
2022 Insulin action and resistance are dependent on a GSK3β-FBXW7-ERRα transcriptional axis. Nature communications 25 35440636
2018 Heme oxygenase metabolites improve astrocytic mitochondrial function via a Ca2+-dependent HIF-1α/ERRα circuit. PloS one 25 30153269
2017 ERRα negatively regulates type I interferon induction by inhibiting TBK1-IRF3 interaction. PLoS pathogens 25 28591144
2014 Effects of estrogen-related receptor alpha (ERRα) on proliferation and metastasis of human lung cancer A549 cells. Journal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban 25 25480584
2012 Mechanism of cardiomyocyte PGC-1α gene regulation by ERRα. Biochemistry and cell biology = Biochimie et biologie cellulaire 25 23668787
2022 Role of HIF-1α/ERRα in Enhancing Cancer Cell Metabolism and Promoting Resistance of Endometrial Cancer Cells to Pyroptosis. Frontiers in oncology 24 35800058
2022 IGF2BP1-regulated expression of ERRα is involved in metabolic reprogramming of chemotherapy resistant osteosarcoma cells. Journal of translational medicine 24 35918761
2021 Estrogen-related receptor alpha (ERRα) is a key regulator of intestinal homeostasis and protects against colitis. Scientific reports 24 34302001
2017 ERRα protein is stabilized by LSD1 in a demethylation-independent manner. PloS one 24 29190800
2016 The PLA2R1-JAK2 pathway upregulates ERRα and its mitochondrial program to exert tumor-suppressive action. Oncogene 24 27041564
2015 Estradiol mediates vasculoprotection via ERRα-dependent regulation of lipid and ROS metabolism in the endothelium. Journal of molecular and cellular cardiology 24 26271712
2016 The Genomic Context and Corecruitment of SP1 Affect ERRα Coactivation by PGC-1α in Muscle Cells. Molecular endocrinology (Baltimore, Md.) 23 27182621
2020 ERRα Expression in Bone Metastases Leads to an Exacerbated Antitumor Immune Response. Cancer research 22 32366476
2019 NURR1 and ERR1 Modulate the Expression of Genes of a DRD2 Coexpression Network Enriched for Schizophrenia Risk. The Journal of neuroscience : the official journal of the Society for Neuroscience 22 31811028
2021 FBXL10 promotes ERRα protein stability and proliferation of breast cancer cells by enhancing the mono-ubiquitylation of ERRα. Cancer letters 21 33450359
2008 Estrogen receptor-related receptor-alpha (ERR-alpha) is dysregulated in inflammatory arthritis. Rheumatology (Oxford, England) 21 18927192
2025 The pro-inflammatory cytokine IL6 suppresses mitochondrial function via the gp130-JAK1/STAT1/3-HIF1α/ERRα axis. Cell reports 20 40056415
2024 Cholesterol biosynthetic pathway induces cellular senescence through ERRα. npj aging 20 38216569
2014 PGC-1α and PGC-1β increase CrT expression and creatine uptake in myotubes via ERRα. Biochimica et biophysica acta 20 25173818
2005 The ERRalpha orphan nuclear receptor controls morphogenetic movements during zebrafish gastrulation. Developmental biology 20 15848392
2022 New insights into cholesterol-mediated ERRα activation in breast cancer progression and pro-tumoral microenvironment orchestration. The FEBS journal 19 36237175
2019 ERRα Regulates OTUB1 Expression to Promote Colorectal Cancer Cell Migration. Journal of Cancer 19 31737118
2023 ERRα protects against sepsis-induced acute lung injury in rats. Molecular medicine (Cambridge, Mass.) 18 37340376
2022 PERM1 regulates energy metabolism in the heart via ERRα/PGC-1α axis. Frontiers in cardiovascular medicine 18 36419485
2008 Conserved properties of a urochordate estrogen receptor-related receptor (ERR) with mammalian ERRalpha. Biochimica et biophysica acta 18 18822397
2023 Ginsenoside Rd, a natural production for attenuating fibrogenesis and inflammation in hepatic fibrosis by regulating the ERRα-mediated P2X7r pathway. Food & function 17 37249244
2022 HPV E6 regulates therapy responses in oropharyngeal cancer by repressing the PGC-1α/ERRα axis. JCI insight 17 36134662
2018 Parkin Modulates ERRα/eNOS Signaling Pathway in Endothelial Cells. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 17 30244249
2024 ZLN005 alleviates PBDE-47 induced impairment of mitochondrial translation and neurotoxicity through PGC-1α/ERRα axis. Journal of hazardous materials 16 38677116
2024 RBBP6-Mediated ERRα Degradation Contributes to Mitochondrial Injury in Renal Tubular Cells in Diabetic Kidney Disease. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 16 39441040
2022 Targeting ERRα promotes cytotoxic effects against acute myeloid leukemia through suppressing mitochondrial oxidative phosphorylation. Journal of hematology & oncology 16 36289517
2021 PI3K/AKT phosphorylation activates ERRα by upregulating PGC‑1α and PGC‑1β in gallbladder cancer. Molecular medicine reports 16 34184087
2020 Increased ABCC4 Expression Induced by ERRα Leads to Docetaxel Resistance via Efflux of Docetaxel in Prostate Cancer. Frontiers in oncology 16 33014785
2020 ERRα promotes pancreatic cancer progression by enhancing the transcription of PAI1 and activating the MEK/ERK pathway. American journal of cancer research 16 33294258

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