FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2417241808> ?p ?o ?g. }

• W2417241808 endingPage "3154" @default.
• W2417241808 startingPage "3144" @default.
• W2417241808 abstract "The pathogenic effect of mutations in the aryl hydrocarbon receptor interacting protein (AIP) gene (AIPmuts) in pituitary adenomas is incompletely understood. We have identified the primary mechanism of loss of function for missense AIPmuts. This study sought to analyze the mechanism/speed of protein turnover of wild-type and missense AIP variants, correlating protein half-life with clinical parameters. Half-life and protein–protein interaction experiments and cross-sectional analysis of AIPmut positive patients' data were performed in a clinical academic research institution. Data were obtained from our cohort of pituitary adenoma patients and literature-reported cases. Protein turnover of endogenous AIP in two cell lines and fifteen AIP variants overexpressed in HEK293 cells was analyzed via cycloheximide chase and proteasome inhibition. Glutathione-S-transferase pull-down and quantitative mass spectrometry identified proteins involved in AIP degradation; results were confirmed by coimmunoprecipitation and gene knockdown. Relevant clinical data was collected. Half-life of wild-type and mutant AIP proteins and its correlation with clinical parameters. Endogenous AIP half-life was similar in HEK293 and lymphoblastoid cells (43.5 and 32.7 h). AIP variants were divided into stable proteins (median, 77.7 h; interquartile range [IQR], 60.7–92.9 h), and those with short (median, 27 h; IQR, 21.6–28.7 h) or very short (median, 7.7 h; IQR, 5.6–10.5 h) half-life; proteasomal inhibition rescued the rapid degradation of mutant proteins. The experimental half-life significantly correlated with age at diagnosis of acromegaly/gigantism (r = 0.411; P = .002). The FBXO3-containing SKP1–CUL1–F-box protein complex was identified as the E3 ubiquitin-ligase recognizing AIP. AIP is a stable protein, driven to ubiquitination by the SKP1–CUL1–F-box protein complex. Enhanced proteasomal degradation is a novel pathogenic mechanism for AIPmuts, with direct implications for the phenotype. We determined that protein instability, leading to shortened protein half-life, is a novel pathogenic mechanism for mutations in the AIP gene with clinical significance for pituitary adenoma patients." @default.
• W2417241808 created "2016-06-24" @default.
• W2417241808 creator A5005900697 @default.
• W2417241808 creator A5008329888 @default.
• W2417241808 creator A5017519053 @default.
• W2417241808 creator A5028039742 @default.
• W2417241808 creator A5050346032 @default.
• W2417241808 creator A5054086194 @default.
• W2417241808 creator A5062205784 @default.
• W2417241808 creator A5062252132 @default.
• W2417241808 creator A5068901036 @default.
• W2417241808 creator A5082443783 @default.
• W2417241808 date "2016-08-01" @default.
• W2417241808 modified "2023-10-16" @default.
• W2417241808 title "Rapid Proteasomal Degradation of Mutant Proteins Is the Primary Mechanism Leading to Tumorigenesis in Patients With Missense<i>AIP</i>Mutations" @default.
• W2417241808 cites W1596200855 @default.
• W2417241808 cites W1925935443 @default.
• W2417241808 cites W1956577542 @default.
• W2417241808 cites W1963776701 @default.
• W2417241808 cites W1969529910 @default.
• W2417241808 cites W1970647532 @default.
• W2417241808 cites W1975609419 @default.
• W2417241808 cites W1975715657 @default.
• W2417241808 cites W1976041483 @default.
• W2417241808 cites W1977403699 @default.
• W2417241808 cites W1980977509 @default.
• W2417241808 cites W1981280101 @default.
• W2417241808 cites W1981875671 @default.
• W2417241808 cites W1997625073 @default.
• W2417241808 cites W2000834746 @default.
• W2417241808 cites W2004802258 @default.
• W2417241808 cites W2007389278 @default.
• W2417241808 cites W2010375889 @default.
• W2417241808 cites W2022156064 @default.
• W2417241808 cites W2040806585 @default.
• W2417241808 cites W2048151136 @default.
• W2417241808 cites W2048829869 @default.
• W2417241808 cites W2049631853 @default.
• W2417241808 cites W2054316167 @default.
• W2417241808 cites W2056195186 @default.
• W2417241808 cites W2063714349 @default.
• W2417241808 cites W2076465180 @default.
• W2417241808 cites W2092189458 @default.
• W2417241808 cites W2094538388 @default.
• W2417241808 cites W2096791516 @default.
• W2417241808 cites W2107607858 @default.
• W2417241808 cites W2112064435 @default.
• W2417241808 cites W2116127657 @default.
• W2417241808 cites W2119882871 @default.
• W2417241808 cites W2120377636 @default.
• W2417241808 cites W2121780718 @default.
• W2417241808 cites W2123383145 @default.
• W2417241808 cites W2128551987 @default.
• W2417241808 cites W2133527431 @default.
• W2417241808 cites W2137423698 @default.
• W2417241808 cites W2137660473 @default.
• W2417241808 cites W2147533449 @default.
• W2417241808 cites W2152280502 @default.
• W2417241808 cites W2156098042 @default.
• W2417241808 cites W2162553759 @default.
• W2417241808 cites W2165887921 @default.
• W2417241808 cites W2167475633 @default.
• W2417241808 cites W2169567789 @default.
• W2417241808 cites W2190745596 @default.
• W2417241808 cites W2325557141 @default.
• W2417241808 cites W3021788942 @default.
• W2417241808 cites W373618616 @default.
• W2417241808 cites W7844153 @default.
• W2417241808 doi "https://doi.org/10.1210/jc.2016-1307" @default.
• W2417241808 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4971335" @default.
• W2417241808 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/27253664" @default.
• W2417241808 hasPublicationYear "2016" @default.
• W2417241808 type Work @default.
• W2417241808 sameAs 2417241808 @default.
• W2417241808 citedByCount "40" @default.
• W2417241808 countsByYear W24172418082015 @default.
• W2417241808 countsByYear W24172418082016 @default.
• W2417241808 countsByYear W24172418082017 @default.
• W2417241808 countsByYear W24172418082018 @default.
• W2417241808 countsByYear W24172418082019 @default.
• W2417241808 countsByYear W24172418082020 @default.
• W2417241808 countsByYear W24172418082021 @default.
• W2417241808 countsByYear W24172418082022 @default.
• W2417241808 countsByYear W24172418082023 @default.
• W2417241808 crossrefType "journal-article" @default.
• W2417241808 hasAuthorship W2417241808A5005900697 @default.
• W2417241808 hasAuthorship W2417241808A5008329888 @default.
• W2417241808 hasAuthorship W2417241808A5017519053 @default.
• W2417241808 hasAuthorship W2417241808A5028039742 @default.
• W2417241808 hasAuthorship W2417241808A5050346032 @default.
• W2417241808 hasAuthorship W2417241808A5054086194 @default.
• W2417241808 hasAuthorship W2417241808A5062205784 @default.
• W2417241808 hasAuthorship W2417241808A5062252132 @default.
• W2417241808 hasAuthorship W2417241808A5068901036 @default.
• W2417241808 hasAuthorship W2417241808A5082443783 @default.
• W2417241808 hasBestOaLocation W24172418081 @default.
• W2417241808 hasConcept C104317684 @default.
• W2417241808 hasConcept C119060515 @default.

• next