FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2890849816> ?p ?o ?g. }

• W2890849816 endingPage "1722" @default.
• W2890849816 startingPage "1708" @default.
• W2890849816 abstract "Thyroid hormone receptors (TRs) are tightly regulated by the corepressors nuclear receptor corepressor (NCoR) and silencing mediator of retinoic acid and thyroid hormone receptors. Three conserved corepressor/NR signature box motifs (CoRNR1-3) forming the nuclear receptor interaction domain have been identified in these corepressors. Whereas TRs regulate multiple normal physiological and developmental pathways, mutations in TRs can result in endocrine diseases and be associated with cancers due to impairment of corepressor release. Three mutants that are located in helix H11 of TRs are of special interest: TRα-M388I, a mutant associated with the development of renal clear cell carcinomas (RCCCs), and TRβ-Δ430 and TRβ-Δ432, two deletion mutants causing resistance to thyroid hormone syndrome.Several cell-based and biophysical methods were used to measure the affinity between wild-type and mutant TRα and TRβ and all the CoRNR motifs from corepressors to quantify the effects of different thyroid hormone analogues on these interactions. This study was coupled with the measurement of interactions between wild-type and mutant TRs in the context of a heterodimer with RXR to a NCoR fragment in the presence of the same ligands. Structural insights into the binding mode of corepressors to TRs were assessed in parallel by nuclear magnetic resonance spectroscopy.The study shows that TRs interact more avidly with the silencing mediator of retinoic acid and thyroid hormone receptors than with NCoR peptides, and that TRα binds most avidly to S-CoRNR3, whereas TRβ binds preferentially to S-CoRNR2. In the studied TR mutants, a transfer of the CoRNR-specificity toward CoRNR1 was observed, coupled with a significant increase in the binding strength. In contrast to 3,5,3'-triiodothyronine (T3), the agonist TRIAC and the antagonist NH-3 were very efficient at dissociating the abnormally strong interactions between mutant TRβs and corepressors. A strong impairment of T3-binding for TRβ mutants was shown compared to TRIAC and NH-3 and could explain the different efficiencies of the different ligands in releasing corepressors from the studied TRβ mutants. Consequently, TRIAC was found to be more effective than T3 in facilitating coactivator recruitment and decreasing the dominant activity of TRβ-Δ430.This study helps to clarify the specific interaction surfaces involved in the pathologic phenotype of TR mutants and demonstrates that TRIAC is a potential therapeutic agent for patients suffering from resistance to thyroid hormone syndromes." @default.
• W2890849816 created "2018-09-27" @default.
• W2890849816 creator A5030536306 @default.
• W2890849816 creator A5037869319 @default.
• W2890849816 creator A5043103834 @default.
• W2890849816 creator A5047452057 @default.
• W2890849816 creator A5048958422 @default.
• W2890849816 creator A5053017306 @default.
• W2890849816 creator A5068776043 @default.
• W2890849816 creator A5074638543 @default.
• W2890849816 creator A5084423309 @default.
• W2890849816 date "2018-12-01" @default.
• W2890849816 modified "2023-10-17" @default.
• W2890849816 title "Pathological Interactions Between Mutant Thyroid Hormone Receptors and Corepressors and Their Modulation by a Thyroid Hormone Analogue with Therapeutic Potential" @default.
• W2890849816 cites W1603742465 @default.
• W2890849816 cites W1971671031 @default.
• W2890849816 cites W1972736309 @default.
• W2890849816 cites W1974915459 @default.
• W2890849816 cites W1975972697 @default.
• W2890849816 cites W1989444478 @default.
• W2890849816 cites W1989830439 @default.
• W2890849816 cites W1995017064 @default.
• W2890849816 cites W2002573435 @default.
• W2890849816 cites W2006920000 @default.
• W2890849816 cites W2009813442 @default.
• W2890849816 cites W2013582920 @default.
• W2890849816 cites W2014644506 @default.
• W2890849816 cites W2020453213 @default.
• W2890849816 cites W2026229582 @default.
• W2890849816 cites W2026930722 @default.
• W2890849816 cites W2029081844 @default.
• W2890849816 cites W2030487145 @default.
• W2890849816 cites W2037310970 @default.
• W2890849816 cites W2047132220 @default.
• W2890849816 cites W2050743111 @default.
• W2890849816 cites W2051997302 @default.
• W2890849816 cites W2061151008 @default.
• W2890849816 cites W2061357909 @default.
• W2890849816 cites W2064935037 @default.
• W2890849816 cites W2065283382 @default.
• W2890849816 cites W2069532898 @default.
• W2890849816 cites W2076755375 @default.
• W2890849816 cites W2082176639 @default.
• W2890849816 cites W2082368668 @default.
• W2890849816 cites W2085997746 @default.
• W2890849816 cites W2087588579 @default.
• W2890849816 cites W2090775250 @default.
• W2890849816 cites W2114520383 @default.
• W2890849816 cites W2118552522 @default.
• W2890849816 cites W2119119522 @default.
• W2890849816 cites W2135338948 @default.
• W2890849816 cites W2138331081 @default.
• W2890849816 cites W2140177311 @default.
• W2890849816 cites W2141033511 @default.
• W2890849816 cites W2141262432 @default.
• W2890849816 cites W2144495921 @default.
• W2890849816 cites W2146073537 @default.
• W2890849816 cites W2148248538 @default.
• W2890849816 cites W2156268135 @default.
• W2890849816 cites W2156281856 @default.
• W2890849816 cites W2156620408 @default.
• W2890849816 cites W2167785149 @default.
• W2890849816 cites W2170170098 @default.
• W2890849816 cites W2598165711 @default.
• W2890849816 cites W2621151172 @default.
• W2890849816 cites W4229958257 @default.
• W2890849816 cites W4236943330 @default.
• W2890849816 cites W55321358 @default.
• W2890849816 doi "https://doi.org/10.1089/thy.2017.0551" @default.
• W2890849816 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30235988" @default.
• W2890849816 hasPublicationYear "2018" @default.
• W2890849816 type Work @default.
• W2890849816 sameAs 2890849816 @default.
• W2890849816 citedByCount "7" @default.
• W2890849816 countsByYear W28908498162018 @default.
• W2890849816 countsByYear W28908498162019 @default.
• W2890849816 countsByYear W28908498162020 @default.
• W2890849816 countsByYear W28908498162021 @default.
• W2890849816 countsByYear W28908498162022 @default.
• W2890849816 crossrefType "journal-article" @default.
• W2890849816 hasAuthorship W2890849816A5030536306 @default.
• W2890849816 hasAuthorship W2890849816A5037869319 @default.
• W2890849816 hasAuthorship W2890849816A5043103834 @default.
• W2890849816 hasAuthorship W2890849816A5047452057 @default.
• W2890849816 hasAuthorship W2890849816A5048958422 @default.
• W2890849816 hasAuthorship W2890849816A5053017306 @default.
• W2890849816 hasAuthorship W2890849816A5068776043 @default.
• W2890849816 hasAuthorship W2890849816A5074638543 @default.
• W2890849816 hasAuthorship W2890849816A5084423309 @default.
• W2890849816 hasConcept C104317684 @default.
• W2890849816 hasConcept C109115496 @default.
• W2890849816 hasConcept C121608353 @default.
• W2890849816 hasConcept C126322002 @default.
• W2890849816 hasConcept C134018914 @default.
• W2890849816 hasConcept C146777309 @default.
• W2890849816 hasConcept C149574134 @default.
• W2890849816 hasConcept C170493617 @default.
• W2890849816 hasConcept C23589133 @default.

• next