FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2740098477> ?p ?o ?g. }

• W2740098477 abstract "Glioblastoma can avoid immune surveillance and induce tumor tolerance, through inhibitory molecules, e.g. PD-L1. Ionizing radiation (IR), used to treat this tumor, is known to increase tumor expression of PD-L1, thus inducing resistance mechanisms. Finding molecular determinants involved in IR-induced PD-L1 may provide a target for preventing such an effect and improve radiotherapy outcomes. We demonstrated that the short isoform of the cochaperone FKBP51 (FKBP51s) regulated PD-L1 expression in melanoma. In glioma, FKBP51s was expressed at high levels, together with PD-L1 and its silencing reduced PD-L1 levels. Conversely, overexpression of FKBP51s increased PD-L1. Different PD-L1 isoforms were observed by immunoblot. A lower band (~37 kDa) corresponding to the naive protein and two upper bands (~50, ~68 kDa) ascribable to post-translationally modified isoforms. FKBP51s was found mainly bound to the heaviest bands of PD-L1, reasonably mature protein, while the canonical isoform FKBP51 appeared to bind only the naive protein. Mature PD-L1 protein consists in carbohydrates addition, the principal chemical modification to most plasma membrane proteins, and, particularly, N-glycosylation. Treatment of immunoprecipitated PD-L1 protein with PNGaseF produced a decrease of the highest band and the appearance of a lower band, corresponding to the naive PD-L1, in accordance with the concept that the heaviest band of PD-L1 is a glycosylated form. Moreover, following subcellular fractionation to obtain extracts from ER and Golgi compartments, we found that naive 37 kDa PD-L1 was detectable in the ER, but not in the Golgi. The PD-L1 glycosylated band was expressed in ER in a small proportion and mostly in the Golgi. FKBP51s, but not the canonical FKBP51, was found in ER. Co-IP of FKBP51s and PD-L1 from ER extract confirmed the two proteins interacted each other in ER. Our results show that naive PD-L1 colocalized in the ER of glioma cell complexed with FKBP51s, while the PD-L1 glycosylated form was measured in the Golgi apparatus. Treatment of glioma cell with increasing doses of IR upregulated PD-L1 expression, in a dose-response manner. Particularly, we found a significant increase in PD-L1 expression at 4 and 8 Gy, in comparison with unirradiated glioma cell. Moreover, IR induction of mature PD-L1 was efficiently counteracted by FKBP51s silencing. Subcellular fractionation of glioma cell subjected to IR in kinetics showed an early and transitory decrease in FKBP51s ER levels at 3hrs, in line with a reduction of the glycosylated band in the whole lysate. After 8 hrs from IR, FKBP51s rose up again in the ER inducing a full maturation of PD-L1. These findings suggested that FKBP51s has a role in catalyzing PD-L1 folding, an essential step to glycosylation, through which it controls the affinity for PD1. This study identifies FKBP51s as an essential element that regulates PD-L1 expression on glioma cell, which is exploited by the tumor to resist to IR. Citation Format: Paolo D9Arrigo, Michele Russo, Elia Guadagno, Roberto Pacelli, Maria Laura Del Basso De caro, Anna Rea, Martina Tufano, Stefania Staibano, Gennaro Ilardi, Maria Fiammetta Romano, Simona Romano. Ionizing radiation-induced PD-L1 upregulation in glioma: a crucial role for the molecular chaperone FKBP5 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 586. doi:10.1158/1538-7445.AM2017-586" @default.
• W2740098477 created "2017-08-08" @default.
• W2740098477 creator A5025655869 @default.
• W2740098477 creator A5027952276 @default.
• W2740098477 creator A5028419934 @default.
• W2740098477 creator A5047387182 @default.
• W2740098477 creator A5070952651 @default.
• W2740098477 creator A5071357354 @default.
• W2740098477 creator A5073840390 @default.
• W2740098477 creator A5074816172 @default.
• W2740098477 creator A5085484614 @default.
• W2740098477 creator A5085795444 @default.
• W2740098477 creator A5088962032 @default.
• W2740098477 date "2017-07-01" @default.
• W2740098477 modified "2023-09-25" @default.
• W2740098477 title "Abstract 586: Ionizing radiation-induced PD-L1 upregulation in glioma: a crucial role for the molecular chaperone FKBP5" @default.
• W2740098477 doi "https://doi.org/10.1158/1538-7445.am2017-586" @default.
• W2740098477 hasPublicationYear "2017" @default.
• W2740098477 type Work @default.
• W2740098477 sameAs 2740098477 @default.
• W2740098477 citedByCount "0" @default.
• W2740098477 crossrefType "proceedings-article" @default.
• W2740098477 hasAuthorship W2740098477A5025655869 @default.
• W2740098477 hasAuthorship W2740098477A5027952276 @default.
• W2740098477 hasAuthorship W2740098477A5028419934 @default.
• W2740098477 hasAuthorship W2740098477A5047387182 @default.
• W2740098477 hasAuthorship W2740098477A5070952651 @default.
• W2740098477 hasAuthorship W2740098477A5071357354 @default.
• W2740098477 hasAuthorship W2740098477A5073840390 @default.
• W2740098477 hasAuthorship W2740098477A5074816172 @default.
• W2740098477 hasAuthorship W2740098477A5085484614 @default.
• W2740098477 hasAuthorship W2740098477A5085795444 @default.
• W2740098477 hasAuthorship W2740098477A5088962032 @default.
• W2740098477 hasConcept C104317684 @default.
• W2740098477 hasConcept C119062480 @default.
• W2740098477 hasConcept C127561419 @default.
• W2740098477 hasConcept C142724271 @default.
• W2740098477 hasConcept C153911025 @default.
• W2740098477 hasConcept C158617107 @default.
• W2740098477 hasConcept C181199279 @default.
• W2740098477 hasConcept C185592680 @default.
• W2740098477 hasConcept C203014093 @default.
• W2740098477 hasConcept C27239569 @default.
• W2740098477 hasConcept C2775962898 @default.
• W2740098477 hasConcept C2777313579 @default.
• W2740098477 hasConcept C2777701055 @default.
• W2740098477 hasConcept C2778227246 @default.
• W2740098477 hasConcept C2781053074 @default.
• W2740098477 hasConcept C502942594 @default.
• W2740098477 hasConcept C53345823 @default.
• W2740098477 hasConcept C55493867 @default.
• W2740098477 hasConcept C71829478 @default.
• W2740098477 hasConcept C71924100 @default.
• W2740098477 hasConcept C86803240 @default.
• W2740098477 hasConcept C8891405 @default.
• W2740098477 hasConcept C95444343 @default.
• W2740098477 hasConceptScore W2740098477C104317684 @default.
• W2740098477 hasConceptScore W2740098477C119062480 @default.
• W2740098477 hasConceptScore W2740098477C127561419 @default.
• W2740098477 hasConceptScore W2740098477C142724271 @default.
• W2740098477 hasConceptScore W2740098477C153911025 @default.
• W2740098477 hasConceptScore W2740098477C158617107 @default.
• W2740098477 hasConceptScore W2740098477C181199279 @default.
• W2740098477 hasConceptScore W2740098477C185592680 @default.
• W2740098477 hasConceptScore W2740098477C203014093 @default.
• W2740098477 hasConceptScore W2740098477C27239569 @default.
• W2740098477 hasConceptScore W2740098477C2775962898 @default.
• W2740098477 hasConceptScore W2740098477C2777313579 @default.
• W2740098477 hasConceptScore W2740098477C2777701055 @default.
• W2740098477 hasConceptScore W2740098477C2778227246 @default.
• W2740098477 hasConceptScore W2740098477C2781053074 @default.
• W2740098477 hasConceptScore W2740098477C502942594 @default.
• W2740098477 hasConceptScore W2740098477C53345823 @default.
• W2740098477 hasConceptScore W2740098477C55493867 @default.
• W2740098477 hasConceptScore W2740098477C71829478 @default.
• W2740098477 hasConceptScore W2740098477C71924100 @default.
• W2740098477 hasConceptScore W2740098477C86803240 @default.
• W2740098477 hasConceptScore W2740098477C8891405 @default.
• W2740098477 hasConceptScore W2740098477C95444343 @default.
• W2740098477 hasLocation W27400984771 @default.
• W2740098477 hasOpenAccess W2740098477 @default.
• W2740098477 hasPrimaryLocation W27400984771 @default.
• W2740098477 hasRelatedWork W1980135696 @default.
• W2740098477 hasRelatedWork W1981866788 @default.
• W2740098477 hasRelatedWork W1990143710 @default.
• W2740098477 hasRelatedWork W2004723089 @default.
• W2740098477 hasRelatedWork W2037842009 @default.
• W2740098477 hasRelatedWork W2042096367 @default.
• W2740098477 hasRelatedWork W2066172043 @default.
• W2740098477 hasRelatedWork W2088400705 @default.
• W2740098477 hasRelatedWork W2156924307 @default.
• W2740098477 hasRelatedWork W2320758087 @default.
• W2740098477 hasRelatedWork W2416482418 @default.
• W2740098477 hasRelatedWork W2419246480 @default.
• W2740098477 hasRelatedWork W24217291 @default.
• W2740098477 hasRelatedWork W2588693818 @default.
• W2740098477 hasRelatedWork W2739109963 @default.
• W2740098477 hasRelatedWork W2981389538 @default.
• W2740098477 hasRelatedWork W3006036897 @default.
• W2740098477 hasRelatedWork W3014462981 @default.

• next