ArticleThe Journal of biological chemistry2010
Novel polymorphisms of nuclear receptor SHP associated with functional and structural changes.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 42 citations in OpenAlex.
- Impact of Pregnancy and Vitamin A Supplementation on CYP2D6 Activity.Journal of clinical pharmacology · 2023Trial
- Mutation in the Common Docking Domain Affects MAP Kinase ERK2 Catalysis and Stability.Cancers · 2023Article
- Analysis and Interpretation of the Impact of Missense Variants in Cancer.International journal of molecular sciences · 2021Review
- Repression of hepatocyte nuclear factor 4 alpha by AP-1 underlies dyslipidemia associated with retinoic acid.Journal of lipid research · 2019Article
- H19 potentiates let-7 family expression through reducing PTBP1 binding to their precursors in cholestasis.Cell death & disease · 2019Article
- H19 Is Expressed in Hybrid Hepatocyte Nuclear Factor 4αHepatology communications · 2018Article
- Loss of PDK4 switches the hepatic NF-κB/TNF pathway from pro-survival to pro-apoptosis.Hepatology (Baltimore, Md.) · 2018Article
- MicroRNA-26-5p functions as a new inhibitor of hepatoblastoma by repressing lin-28 homolog B and aurora kinase a expression.Hepatology communications · 2018Article
- Farnesoid X receptor signaling activates the hepatic X-box binding protein 1 pathway in vitro and in mice.Hepatology (Baltimore, Md.) · 2018Article
- Deficiency of pyruvate dehydrogenase kinase 4 sensitizes mouse liver to diethylnitrosamine and arsenic toxicity through inducing apoptosis.Liver research (Beijing, China) · 2018Article
- H19 promotes cholestatic liver fibrosis by preventing ZEB1-mediated inhibition of epithelial cell adhesion molecule.Hepatology (Baltimore, Md.) · 2017Article
- High-mobility-group protein 2 regulated by microRNA-127 and small heterodimer partner modulates pluripotency of mouse embryonic stem cells and liver tumor initiating cells.Hepatology communications · 2017Article
- Pyruvate Dehydrogenase Kinase 4 Deficiency Results in Expedited Cellular Proliferation through E2F1-Mediated Increase of Cyclins.Molecular pharmacology · 2017Article
- Long noncoding RNA MEG3 induces cholestatic liver injury by interaction with PTBP1 to facilitate shp mRNA decay.Hepatology (Baltimore, Md.) · 2017Article
- Transcriptional Regulation of CYP2D6 Expression.Drug metabolism and disposition: the biological fate of chemicals · 2017Review
- Metabolomics Analysis Revealed Distinct Cyclic Changes of Metabolites Altered by Chronic Ethanol-Plus-Binge and Shp Deficiency.Alcoholism, clinical and experimental research · 2016Article
- REV-ERBα Activates C/EBP Homologous Protein to Control Small Heterodimer Partner-Mediated Oscillation of Alcoholic Fatty Liver.The American journal of pathology · 2016Article
- A Novel Small Molecule Activator of Nuclear Receptor SHP Inhibits HCC Cell Migration via Suppressing Ccl2.Molecular cancer therapeutics · 2016Article
- Arsenic silences hepatic PDK4 expression through activation of histone H3K9 methylatransferase G9a.Toxicology and applied pharmacology · 2016Article
- Peptidic degron in EID1 is recognized by an SCF E3 ligase complex containing the orphan F-box protein FBXO21.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
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Authors and funding
9 authors at 5 institutions in 4 countries.
Funding
Abstract
We identified three heterozygous nonsynonymous single nucleotide polymorphisms in the small heterodimer partner (SHP, NROB2) gene in normal subjects and CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy)-like patients, including two novel missense mutations (p.R38H, p.K170N) and one of the previously reported polymorphism (p.G171A). Four novel heterozygous mutations were also identified in the intron ((Intron)1265T-->A), 3'-untranslated region ((3'-UTR)101C-->G, (3'-UTR)186T-->C), and promoter ((Pro)-423C-->T) of the SHP gene. The exonic R38H and K170N mutants exhibited impaired nuclear translocation. K170N made SHP more susceptible to ubiquitination mediated degradation and blocked SHP acetylation, which displayed lost repressive activity on its interacting partners ERRgamma and HNF4alpha but not LRH-1. In contrast, G171A increased SHP mRNA and protein expression and maintained normal function. In general, the interaction of SHP mutants with LRH-1 and EID1 was enhanced. K170N also markedly impaired the recruitment of SHP, HNF4alpha, HDAC1, and HDAC3 to the apoCIII promoter. Molecular dynamics simulations of SHP showed that G171A stabilized the nuclear receptor boxes, whereas K170N promoted the conformational destabilization of all the structural elements of the receptor. This study suggests that genetic variations in SHP are common among human subjects and the Lys-170 residue plays a key role in controlling SHP ubiquitination and acetylation associated with SHP protein stability and repressive function.
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