Matches in SemOpenAlex for { <https://semopenalex.org/work/W2890449372> ?p ?o ?g. }
- W2890449372 abstract "ABSTRACT The PERK arm of the unfolded protein response (UPR) regulates cellular proteostasis and survival in response to endoplasmic reticulum (ER) stress. However, the impact of PERK signaling on extracellular proteostasis is poorly understood. We define how PERK signaling influences extracellular proteostasis during ER stress using a conformational reporter of the secreted amyloidogenic protein transthyretin (TTR). We show that inhibiting PERK signaling impairs ER stress-dependent secretion of destabilized TTR by increasing its ER retention in chaperone-bound complexes. Interestingly, PERK inhibition promotes the ER stress-dependent secretion of TTR in non-native conformations that accumulate extracellularly as soluble oligomers. Pharmacologic or genetic TTR stabilization partially restores secretion of native TTR tetramers. However, PERK inhibition still increases the ER stress-dependent secretion of TTR in non-native conformations under these conditions, indicating that the conformation of stable secreted proteins can also be affected by inhibiting PERK. Our results define a role for PERK in regulating extracellular proteostasis during ER stress and indicate that genetic or aging-related alterations in PERK signaling can exacerbate ER stress-related imbalances in extracellular proteostasis implicated in diverse diseases." @default.
- W2890449372 created "2018-09-27" @default.
- W2890449372 creator A5089122118 @default.
- W2890449372 creator A5091837670 @default.
- W2890449372 date "2018-09-17" @default.
- W2890449372 modified "2023-09-23" @default.
- W2890449372 title "PERK Signaling Regulates Extracellular Proteostasis of an Amyloidogenic Protein During Endoplasmic Reticulum Stress" @default.
- W2890449372 cites W1505761263 @default.
- W2890449372 cites W1856496738 @default.
- W2890449372 cites W1970195253 @default.
- W2890449372 cites W1970500983 @default.
- W2890449372 cites W1980438612 @default.
- W2890449372 cites W1992898664 @default.
- W2890449372 cites W1994772574 @default.
- W2890449372 cites W1996826558 @default.
- W2890449372 cites W1997464771 @default.
- W2890449372 cites W2019261756 @default.
- W2890449372 cites W2026208013 @default.
- W2890449372 cites W2046431795 @default.
- W2890449372 cites W2048551040 @default.
- W2890449372 cites W2050252352 @default.
- W2890449372 cites W2050664140 @default.
- W2890449372 cites W2053588758 @default.
- W2890449372 cites W2067040999 @default.
- W2890449372 cites W2068854526 @default.
- W2890449372 cites W2073503225 @default.
- W2890449372 cites W2077784911 @default.
- W2890449372 cites W2085201901 @default.
- W2890449372 cites W2100472948 @default.
- W2890449372 cites W2102049218 @default.
- W2890449372 cites W2108252761 @default.
- W2890449372 cites W2119902047 @default.
- W2890449372 cites W2120736516 @default.
- W2890449372 cites W2127848114 @default.
- W2890449372 cites W2131632095 @default.
- W2890449372 cites W2147646344 @default.
- W2890449372 cites W2160966221 @default.
- W2890449372 cites W2163285372 @default.
- W2890449372 cites W2281508633 @default.
- W2890449372 cites W2531576435 @default.
- W2890449372 cites W2583987092 @default.
- W2890449372 cites W2609546453 @default.
- W2890449372 cites W2726888143 @default.
- W2890449372 cites W2738794221 @default.
- W2890449372 cites W2760206834 @default.
- W2890449372 cites W2766138174 @default.
- W2890449372 cites W2766900039 @default.
- W2890449372 cites W2783338206 @default.
- W2890449372 cites W2786412717 @default.
- W2890449372 cites W2793107637 @default.
- W2890449372 cites W2793262607 @default.
- W2890449372 cites W2888537636 @default.
- W2890449372 doi "https://doi.org/10.1101/419564" @default.
- W2890449372 hasPublicationYear "2018" @default.
- W2890449372 type Work @default.
- W2890449372 sameAs 2890449372 @default.
- W2890449372 citedByCount "0" @default.
- W2890449372 crossrefType "posted-content" @default.
- W2890449372 hasAuthorship W2890449372A5089122118 @default.
- W2890449372 hasAuthorship W2890449372A5091837670 @default.
- W2890449372 hasBestOaLocation W28904493721 @default.
- W2890449372 hasConcept C139447449 @default.
- W2890449372 hasConcept C156399914 @default.
- W2890449372 hasConcept C158617107 @default.
- W2890449372 hasConcept C185592680 @default.
- W2890449372 hasConcept C204328495 @default.
- W2890449372 hasConcept C2781452922 @default.
- W2890449372 hasConcept C28406088 @default.
- W2890449372 hasConcept C49039625 @default.
- W2890449372 hasConcept C55493867 @default.
- W2890449372 hasConcept C86803240 @default.
- W2890449372 hasConcept C95444343 @default.
- W2890449372 hasConceptScore W2890449372C139447449 @default.
- W2890449372 hasConceptScore W2890449372C156399914 @default.
- W2890449372 hasConceptScore W2890449372C158617107 @default.
- W2890449372 hasConceptScore W2890449372C185592680 @default.
- W2890449372 hasConceptScore W2890449372C204328495 @default.
- W2890449372 hasConceptScore W2890449372C2781452922 @default.
- W2890449372 hasConceptScore W2890449372C28406088 @default.
- W2890449372 hasConceptScore W2890449372C49039625 @default.
- W2890449372 hasConceptScore W2890449372C55493867 @default.
- W2890449372 hasConceptScore W2890449372C86803240 @default.
- W2890449372 hasConceptScore W2890449372C95444343 @default.
- W2890449372 hasLocation W28904493721 @default.
- W2890449372 hasLocation W28904493722 @default.
- W2890449372 hasLocation W28904493723 @default.
- W2890449372 hasOpenAccess W2890449372 @default.
- W2890449372 hasPrimaryLocation W28904493721 @default.
- W2890449372 hasRelatedWork W1986164963 @default.
- W2890449372 hasRelatedWork W1995856381 @default.
- W2890449372 hasRelatedWork W2423726595 @default.
- W2890449372 hasRelatedWork W2531576435 @default.
- W2890449372 hasRelatedWork W2755938890 @default.
- W2890449372 hasRelatedWork W2769783328 @default.
- W2890449372 hasRelatedWork W2790736181 @default.
- W2890449372 hasRelatedWork W2890449372 @default.
- W2890449372 hasRelatedWork W2951221898 @default.
- W2890449372 hasRelatedWork W3084262678 @default.
- W2890449372 isParatext "false" @default.
- W2890449372 isRetracted "false" @default.