FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2322270922> ?p ?o ?g. }

• W2322270922 endingPage "11322" @default.
• W2322270922 startingPage "11313" @default.
• W2322270922 abstract "INS-VNTR (insulin-variable number of tandem repeats) and AIRE (autoimmune regulator) have been associated with the modulation of insulin gene expression in thymus, which is essential to induce either insulin tolerance or the development of insulin autoimmunity and type 1 diabetes. We sought to analyze whether each functional domain of AIRE is critical for the activation of INS-VNTR in human thymic epithelial cells. Twelve missense or nonsense mutations in AIRE and two chimeric AIRE constructs were generated. A luciferase reporter assay and a pulldown assay using biotinylated INS-class I VNTR probe were performed to examine the transactivation and binding activities of WT, mutant, and chimeric AIREs on the INS-VNTR promoter. Confocal microscopy analysis was performed for WT or mutant AIRE cellular localization. We found that all of the AIRE mutations resulted in loss of transcriptional activation of INS-VNTR except mutant P252L. Using WT/mutant AIRE heterozygous forms to modulate the INS-VNTR target revealed five mutations (R257X, G228W, C311fsX376, L397fsX478, and R433fsX502) that functioned in a dominant negative fashion. The LXXLL-3 motif is identified for the first time to be essential for DNA binding to INS-VNTR, whereas the intact PHD1, PHD2, LXXLL-3, and LXXLL-4 motifs were important for successful transcriptional activation. AIRE nuclear localization in the human thymic epithelial cell line was disrupted by mutations in the homogenously staining region domain and the R257X mutation in the PHD1 domain. This study supports the notion that AIRE mutation could specifically affect human insulin gene expression in thymic epithelial cells through INS-VNTR and subsequently induce either insulin tolerance or autoimmunity. INS-VNTR (insulin-variable number of tandem repeats) and AIRE (autoimmune regulator) have been associated with the modulation of insulin gene expression in thymus, which is essential to induce either insulin tolerance or the development of insulin autoimmunity and type 1 diabetes. We sought to analyze whether each functional domain of AIRE is critical for the activation of INS-VNTR in human thymic epithelial cells. Twelve missense or nonsense mutations in AIRE and two chimeric AIRE constructs were generated. A luciferase reporter assay and a pulldown assay using biotinylated INS-class I VNTR probe were performed to examine the transactivation and binding activities of WT, mutant, and chimeric AIREs on the INS-VNTR promoter. Confocal microscopy analysis was performed for WT or mutant AIRE cellular localization. We found that all of the AIRE mutations resulted in loss of transcriptional activation of INS-VNTR except mutant P252L. Using WT/mutant AIRE heterozygous forms to modulate the INS-VNTR target revealed five mutations (R257X, G228W, C311fsX376, L397fsX478, and R433fsX502) that functioned in a dominant negative fashion. The LXXLL-3 motif is identified for the first time to be essential for DNA binding to INS-VNTR, whereas the intact PHD1, PHD2, LXXLL-3, and LXXLL-4 motifs were important for successful transcriptional activation. AIRE nuclear localization in the human thymic epithelial cell line was disrupted by mutations in the homogenously staining region domain and the R257X mutation in the PHD1 domain. This study supports the notion that AIRE mutation could specifically affect human insulin gene expression in thymic epithelial cells through INS-VNTR and subsequently induce either insulin tolerance or autoimmunity." @default.
• W2322270922 created "2016-06-24" @default.
• W2322270922 creator A5004492371 @default.
• W2322270922 creator A5031611361 @default.
• W2322270922 creator A5040758427 @default.
• W2322270922 creator A5049523575 @default.
• W2322270922 date "2016-05-01" @default.
• W2322270922 modified "2023-09-29" @default.
• W2322270922 title "Functional Domains of Autoimmune Regulator (AIRE) Modulate INS-VNTR Transcription in Human Thymic Epithelial Cells" @default.
• W2322270922 cites W1501286679 @default.
• W2322270922 cites W1844353938 @default.
• W2322270922 cites W1971185090 @default.
• W2322270922 cites W1977207493 @default.
• W2322270922 cites W1978774430 @default.
• W2322270922 cites W1982569530 @default.
• W2322270922 cites W1985843482 @default.
• W2322270922 cites W1989321724 @default.
• W2322270922 cites W1998905180 @default.
• W2322270922 cites W1999417890 @default.
• W2322270922 cites W2009759884 @default.
• W2322270922 cites W2011254270 @default.
• W2322270922 cites W2016131549 @default.
• W2322270922 cites W2022807116 @default.
• W2322270922 cites W2025929993 @default.
• W2322270922 cites W2027240299 @default.
• W2322270922 cites W2028222510 @default.
• W2322270922 cites W2033441651 @default.
• W2322270922 cites W2048284172 @default.
• W2322270922 cites W2051346727 @default.
• W2322270922 cites W2063733110 @default.
• W2322270922 cites W2063802283 @default.
• W2322270922 cites W2065446100 @default.
• W2322270922 cites W2070972996 @default.
• W2322270922 cites W2083737302 @default.
• W2322270922 cites W2084325574 @default.
• W2322270922 cites W2085567045 @default.
• W2322270922 cites W2095315030 @default.
• W2322270922 cites W2103263790 @default.
• W2322270922 cites W2106850730 @default.
• W2322270922 cites W2114154686 @default.
• W2322270922 cites W2114944802 @default.
• W2322270922 cites W2115771911 @default.
• W2322270922 cites W2130784093 @default.
• W2322270922 cites W2155964470 @default.
• W2322270922 cites W2160127445 @default.
• W2322270922 cites W2165214298 @default.
• W2322270922 cites W2270521400 @default.
• W2322270922 cites W2331919277 @default.
• W2322270922 doi "https://doi.org/10.1074/jbc.m116.722488" @default.
• W2322270922 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4900276" @default.
• W2322270922 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/27048654" @default.
• W2322270922 hasPublicationYear "2016" @default.
• W2322270922 type Work @default.
• W2322270922 sameAs 2322270922 @default.
• W2322270922 citedByCount "14" @default.
• W2322270922 countsByYear W23222709222016 @default.
• W2322270922 countsByYear W23222709222018 @default.
• W2322270922 countsByYear W23222709222019 @default.
• W2322270922 countsByYear W23222709222020 @default.
• W2322270922 countsByYear W23222709222021 @default.
• W2322270922 countsByYear W23222709222022 @default.
• W2322270922 countsByYear W23222709222023 @default.
• W2322270922 crossrefType "journal-article" @default.
• W2322270922 hasAuthorship W2322270922A5004492371 @default.
• W2322270922 hasAuthorship W2322270922A5031611361 @default.
• W2322270922 hasAuthorship W2322270922A5040758427 @default.
• W2322270922 hasAuthorship W2322270922A5049523575 @default.
• W2322270922 hasBestOaLocation W23222709221 @default.
• W2322270922 hasConcept C104317684 @default.
• W2322270922 hasConcept C123894998 @default.
• W2322270922 hasConcept C1292079 @default.
• W2322270922 hasConcept C143065580 @default.
• W2322270922 hasConcept C153911025 @default.
• W2322270922 hasConcept C2776566471 @default.
• W2322270922 hasConcept C33987129 @default.
• W2322270922 hasConcept C40767141 @default.
• W2322270922 hasConcept C501734568 @default.
• W2322270922 hasConcept C54355233 @default.
• W2322270922 hasConcept C6929976 @default.
• W2322270922 hasConcept C75563809 @default.
• W2322270922 hasConcept C86339819 @default.
• W2322270922 hasConcept C86803240 @default.
• W2322270922 hasConcept C95444343 @default.
• W2322270922 hasConcept C96777560 @default.
• W2322270922 hasConceptScore W2322270922C104317684 @default.
• W2322270922 hasConceptScore W2322270922C123894998 @default.
• W2322270922 hasConceptScore W2322270922C1292079 @default.
• W2322270922 hasConceptScore W2322270922C143065580 @default.
• W2322270922 hasConceptScore W2322270922C153911025 @default.
• W2322270922 hasConceptScore W2322270922C2776566471 @default.
• W2322270922 hasConceptScore W2322270922C33987129 @default.
• W2322270922 hasConceptScore W2322270922C40767141 @default.
• W2322270922 hasConceptScore W2322270922C501734568 @default.
• W2322270922 hasConceptScore W2322270922C54355233 @default.
• W2322270922 hasConceptScore W2322270922C6929976 @default.
• W2322270922 hasConceptScore W2322270922C75563809 @default.
• W2322270922 hasConceptScore W2322270922C86339819 @default.
• W2322270922 hasConceptScore W2322270922C86803240 @default.

• next