ArticleMolecular endocrinology (Baltimore, Md.)2008
Phosphorylation-dependent sumoylation regulates estrogen-related receptor-alpha and -gamma transcriptional activity through a synergy control motif.
Article in Molecular endocrinology (Baltimore, Md.), 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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Who cites it
61 citing papers in PubMed, 99 citations in OpenAlex.
- Role of nuclear receptors, lipid metabolism, and mitochondrial function in the pathogenesis of diabetic kidney disease.American journal of physiology. Renal physiology · 2025Review
- PGC-1α Activation by Polyphenols: A Pathway to Thermogenesis.Molecular nutrition & food research · 2025Review
- Estrogen-Related Receptor α: A Key Transcription Factor in the Regulation of Energy Metabolism at an Organismic Level and a Target of the ABA/LANCL Hormone Receptor System.International journal of molecular sciences · 2024Review
- ERRα: unraveling its role as a key player in cell migration.Oncogene · 2024Review
- International Union of Basic and Clinical Pharmacology CXIII: Nuclear Receptor Superfamily-Update 2023.Pharmacological reviews · 2023Review
- A NovelMicroorganisms · 2023Article
- Estrogen-related Receptor Signaling in Skeletal Muscle Fitness.International journal of sports medicine · 2023Article
- Innately expressed estrogen-related receptors in the skeletal muscle are indispensable for exercise fitness.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2023Article
- Roles of Estrogen, Estrogen Receptors, and Estrogen-Related Receptors in Skeletal Muscle: Regulation of Mitochondrial Function.International journal of molecular sciences · 2023Review
- PGC-1β and ERRα Promote Glutamine Metabolism and Colorectal Cancer Survival via Transcriptional Upregulation of PCK2.Cancers · 2022Article
- Estrogen-related receptor gamma regulates mitochondrial and synaptic genes and modulates vulnerability to synucleinopathy.NPJ Parkinson's disease · 2022Article
- Insulin action and resistance are dependent on a GSK3β-FBXW7-ERRα transcriptional axis.Nature communications · 2022Article
- Molecular dynamics of estrogen-related receptors and their regulatory proteins: roles in transcriptional control for endocrine and metabolic signaling.Anatomical science international · 2022Review
- Subcellular dynamics of estrogen-related receptors involved in transrepression through interactions with scaffold attachment factor B1.Histochemistry and cell biology · 2021Article
- The emerging role of estrogen related receptorα in complications of non-small cell lung cancers.Oncology letters · 2021Review
- Transcriptional Regulation of ROS Homeostasis by the ERR Subfamily of Nuclear Receptors.Antioxidants (Basel, Switzerland) · 2021Review
- Estrogen-related receptors: novel potential regulators of osteoarthritis pathogenesis.Molecular medicine (Cambridge, Mass.) · 2021Review
- Regulation of the expression of the estrogen related receptors (ERRs).Cellular and molecular life sciences : CMLS · 2020Review
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1 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Interplay between different posttranslational modifications of transcription factors is an important mechanism to achieve an integrated regulation of gene expression. For the estrogen-related receptors (ERRs) alpha and gamma, regulation by posttranslational modifications is still poorly documented. Here we show that transcriptional repression associated with the ERR amino-terminal domains is mediated through sumoylation at a conserved phospho-sumoyl switch, psiKxEPxSP, that exists within a larger synergy control motif. Arginine substitution of the sumoylatable lysine residue or alanine substitution of a nearby phosphorylatable serine residue (serine 19 in ERRalpha) increased the transcriptional activity of both ERRalpha and -gamma. In addition, phospho-mimetic substitution of the serine residue with aspartate restored the sumoylation and transcriptional repression activity. The increased transcriptional activity of the sumoylation-deficient mutants was more pronounced in the presence of multiple adjacent ERR response elements. We also identified protein inhibitor of activated signal transducer and activator of transcription y as an interacting partner and a small ubiquitin-related modifier E3 ligase for ERRalpha. Importantly, analysis with a phospho-specific antibody revealed that sumoylation of ERRalpha in mouse liver requires phosphorylation of serine 19. Taken together, these results show that the interplay of phosphorylation and sumoylation in the amino-terminal domain provides an additional mechanism to regulate the transcriptional activity of ERRalpha and -gamma.
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