Matches in SemOpenAlex for { <https://semopenalex.org/work/W3004842068> ?p ?o ?g. }
Showing items 1 to 67 of
67
with 100 items per page.
- W3004842068 endingPage "342a" @default.
- W3004842068 startingPage "342a" @default.
- W3004842068 abstract "Pancreatic and duodenal homeobox 1 (Pdx1) is a homeodomain transcription factor required for pancreatic development and maintenance of glucose homeostasis in β cells. The DNA-binding domain is flanked by two intrinsically disordered regions (IDRs) that contribute to the activation and inhibition of Pdx1. Of particular interest, a short linear motif in the C-terminal disordered domain of Pdx1 (Pdx1-C) is known to interact with speckle-type POZ protein (SPOP) and this interaction contributes to Pdx1 destabilization. SPOP binds targeted substrates via their IDRs and recruits ubiquitin ligase machinery, resulting in polyubiquitination and proteasomal degradation of such substrates. Many SPOP substrates display multiple SPOP-binding motifs (SBMs), which, coupled with the ability of SPOP to self-assemble, contributes to a favorable, multivalent interaction between SPOP and substrate. Using 13C direct-detect NMR methods optimized for intrinsically disordered proteins, our lab identified a second SBM within Pdx1-C. We hypothesized that both established and novel SBMs within Pdx1-C would be required for a functional interaction with SPOP. We used orthogonal biophysical and cell biological approaches to probe the Pdx1-SPOP binding interaction. Each SBM in Pdx1-C binds with relatively weak affinity; however, binding of the entire C-terminus toward SPOP is enhanced nearly 50-fold from the strongest motif alone. Further, our study implicates a new behavior of SPOP toward its substrate proteins in cells. From this, we predict that multivalency-driven liquid-liquid phase separation between SPOP and its substrates will depend on the number of SBMs within a given substrate. Future studies will explore the cellular signals that lead to Pdx1-SPOP interaction in cells and which structural and biochemical features permit such interaction. In this way, we may further understand the mechanisms of Pdx1 destabilization by SPOP." @default.
- W3004842068 created "2020-02-14" @default.
- W3004842068 creator A5020237627 @default.
- W3004842068 creator A5039142010 @default.
- W3004842068 creator A5039479636 @default.
- W3004842068 creator A5047930774 @default.
- W3004842068 creator A5059703816 @default.
- W3004842068 creator A5085540282 @default.
- W3004842068 date "2020-02-01" @default.
- W3004842068 modified "2023-09-26" @default.
- W3004842068 title "Insights into SPOP-Substrate Behavior through Studies of Pdx1-SPOP Interactions" @default.
- W3004842068 doi "https://doi.org/10.1016/j.bpj.2019.11.1902" @default.
- W3004842068 hasPublicationYear "2020" @default.
- W3004842068 type Work @default.
- W3004842068 sameAs 3004842068 @default.
- W3004842068 citedByCount "0" @default.
- W3004842068 crossrefType "journal-article" @default.
- W3004842068 hasAuthorship W3004842068A5020237627 @default.
- W3004842068 hasAuthorship W3004842068A5039142010 @default.
- W3004842068 hasAuthorship W3004842068A5039479636 @default.
- W3004842068 hasAuthorship W3004842068A5047930774 @default.
- W3004842068 hasAuthorship W3004842068A5059703816 @default.
- W3004842068 hasAuthorship W3004842068A5085540282 @default.
- W3004842068 hasBestOaLocation W30048420681 @default.
- W3004842068 hasConcept C104317684 @default.
- W3004842068 hasConcept C12554922 @default.
- W3004842068 hasConcept C134459356 @default.
- W3004842068 hasConcept C185592680 @default.
- W3004842068 hasConcept C25602115 @default.
- W3004842068 hasConcept C2779050171 @default.
- W3004842068 hasConcept C51639874 @default.
- W3004842068 hasConcept C55493867 @default.
- W3004842068 hasConcept C86339819 @default.
- W3004842068 hasConcept C86803240 @default.
- W3004842068 hasConcept C95444343 @default.
- W3004842068 hasConceptScore W3004842068C104317684 @default.
- W3004842068 hasConceptScore W3004842068C12554922 @default.
- W3004842068 hasConceptScore W3004842068C134459356 @default.
- W3004842068 hasConceptScore W3004842068C185592680 @default.
- W3004842068 hasConceptScore W3004842068C25602115 @default.
- W3004842068 hasConceptScore W3004842068C2779050171 @default.
- W3004842068 hasConceptScore W3004842068C51639874 @default.
- W3004842068 hasConceptScore W3004842068C55493867 @default.
- W3004842068 hasConceptScore W3004842068C86339819 @default.
- W3004842068 hasConceptScore W3004842068C86803240 @default.
- W3004842068 hasConceptScore W3004842068C95444343 @default.
- W3004842068 hasIssue "3" @default.
- W3004842068 hasLocation W30048420681 @default.
- W3004842068 hasOpenAccess W3004842068 @default.
- W3004842068 hasPrimaryLocation W30048420681 @default.
- W3004842068 hasRelatedWork W137142808 @default.
- W3004842068 hasRelatedWork W1967904525 @default.
- W3004842068 hasRelatedWork W1975181559 @default.
- W3004842068 hasRelatedWork W2007093894 @default.
- W3004842068 hasRelatedWork W2010461435 @default.
- W3004842068 hasRelatedWork W2040509817 @default.
- W3004842068 hasRelatedWork W2144449542 @default.
- W3004842068 hasRelatedWork W2148426671 @default.
- W3004842068 hasRelatedWork W2901681119 @default.
- W3004842068 hasRelatedWork W4285732750 @default.
- W3004842068 hasVolume "118" @default.
- W3004842068 isParatext "false" @default.
- W3004842068 isRetracted "false" @default.
- W3004842068 magId "3004842068" @default.
- W3004842068 workType "article" @default.