Matches in SemOpenAlex for { <https://semopenalex.org/work/W4200422124> ?p ?o ?g. }
Showing items 1 to 80 of
80
with 100 items per page.
- W4200422124 abstract "Phosphorylation signaling is an essential post-translational regulatory mechanism that governs almost all eukaryotic biological processes and is controlled by an interplay between protein kinases and phosphatases. Knowledge of direct substrates of kinases provides evidence of mechanisms that relate activity to biological function. Linking kinases to their protein substrates can be achieved by inhibiting or reducing kinase activity and quantitative comparisons of phosphoproteomes in the presence and absence of kinase activity. Unfortunately, most of the human kinases lack chemical inhibitors with selectivity required to unambiguously assign protein substrates to their respective kinases. Here, we develop and validate a chemical proteomics strategy for linking kinase activities to protein substrates via targeted protein degradation and quantitative phosphoproteomics and apply it to the well-studied, essential mitotic regulator polo-like kinase 1 (Plk1). We leveraged the Tir1/auxin system to engineer HeLa cells with endogenously homozygous auxin-inducible degron (AID)-Plk1). We used HeLa cells and determined the impact of AID-tagging on Plk1 activity, localization, protein interactors, and substrate motifs. Using quantitative proteomics, we show that of over 8,000 proteins quantified, auxin addition is highly selective for degrading AID-Plk1 in mitotic cells. Comparison of phosphoproteome changes in response to chemical Plk1 inhibition to auxin-induced degradation revealed a striking degree of correlation. Finally, we explored basal protein turnover as a potential basis for clonal differences in auxin-induced degradation rates for AID-Plk1 cells. Taken together, our work provides a roadmap for the application of AID technology as a general strategy for the kinome-wide discovery of kinase-substrate relationships." @default.
- W4200422124 created "2021-12-31" @default.
- W4200422124 creator A5001482747 @default.
- W4200422124 creator A5019829353 @default.
- W4200422124 creator A5035751524 @default.
- W4200422124 creator A5035904151 @default.
- W4200422124 creator A5038086559 @default.
- W4200422124 creator A5043527284 @default.
- W4200422124 creator A5044050308 @default.
- W4200422124 creator A5054886477 @default.
- W4200422124 creator A5089564388 @default.
- W4200422124 date "2021-12-10" @default.
- W4200422124 modified "2023-10-16" @default.
- W4200422124 title "Development and validation of inducible protein degradation and quantitative phosphoproteomics to identify kinase-substrate relationships." @default.
- W4200422124 doi "https://doi.org/10.1101/2021.12.08.471812" @default.
- W4200422124 hasPublicationYear "2021" @default.
- W4200422124 type Work @default.
- W4200422124 citedByCount "1" @default.
- W4200422124 countsByYear W42004221242023 @default.
- W4200422124 crossrefType "posted-content" @default.
- W4200422124 hasAuthorship W4200422124A5001482747 @default.
- W4200422124 hasAuthorship W4200422124A5019829353 @default.
- W4200422124 hasAuthorship W4200422124A5035751524 @default.
- W4200422124 hasAuthorship W4200422124A5035904151 @default.
- W4200422124 hasAuthorship W4200422124A5038086559 @default.
- W4200422124 hasAuthorship W4200422124A5043527284 @default.
- W4200422124 hasAuthorship W4200422124A5044050308 @default.
- W4200422124 hasAuthorship W4200422124A5054886477 @default.
- W4200422124 hasAuthorship W4200422124A5089564388 @default.
- W4200422124 hasBestOaLocation W42004221241 @default.
- W4200422124 hasConcept C104317684 @default.
- W4200422124 hasConcept C11960822 @default.
- W4200422124 hasConcept C146276462 @default.
- W4200422124 hasConcept C1491633281 @default.
- W4200422124 hasConcept C184235292 @default.
- W4200422124 hasConcept C185592680 @default.
- W4200422124 hasConcept C29537977 @default.
- W4200422124 hasConcept C2992195973 @default.
- W4200422124 hasConcept C46111723 @default.
- W4200422124 hasConcept C54174078 @default.
- W4200422124 hasConcept C55493867 @default.
- W4200422124 hasConcept C6675166 @default.
- W4200422124 hasConcept C80311884 @default.
- W4200422124 hasConcept C86803240 @default.
- W4200422124 hasConcept C87325107 @default.
- W4200422124 hasConcept C95444343 @default.
- W4200422124 hasConcept C97029542 @default.
- W4200422124 hasConceptScore W4200422124C104317684 @default.
- W4200422124 hasConceptScore W4200422124C11960822 @default.
- W4200422124 hasConceptScore W4200422124C146276462 @default.
- W4200422124 hasConceptScore W4200422124C1491633281 @default.
- W4200422124 hasConceptScore W4200422124C184235292 @default.
- W4200422124 hasConceptScore W4200422124C185592680 @default.
- W4200422124 hasConceptScore W4200422124C29537977 @default.
- W4200422124 hasConceptScore W4200422124C2992195973 @default.
- W4200422124 hasConceptScore W4200422124C46111723 @default.
- W4200422124 hasConceptScore W4200422124C54174078 @default.
- W4200422124 hasConceptScore W4200422124C55493867 @default.
- W4200422124 hasConceptScore W4200422124C6675166 @default.
- W4200422124 hasConceptScore W4200422124C80311884 @default.
- W4200422124 hasConceptScore W4200422124C86803240 @default.
- W4200422124 hasConceptScore W4200422124C87325107 @default.
- W4200422124 hasConceptScore W4200422124C95444343 @default.
- W4200422124 hasConceptScore W4200422124C97029542 @default.
- W4200422124 hasLocation W42004221241 @default.
- W4200422124 hasOpenAccess W4200422124 @default.
- W4200422124 hasPrimaryLocation W42004221241 @default.
- W4200422124 hasRelatedWork W2004545834 @default.
- W4200422124 hasRelatedWork W2004562122 @default.
- W4200422124 hasRelatedWork W2109482992 @default.
- W4200422124 hasRelatedWork W2611522287 @default.
- W4200422124 hasRelatedWork W2739321151 @default.
- W4200422124 hasRelatedWork W2911789102 @default.
- W4200422124 hasRelatedWork W2949607482 @default.
- W4200422124 hasRelatedWork W3006392649 @default.
- W4200422124 hasRelatedWork W4200422124 @default.
- W4200422124 hasRelatedWork W4302288080 @default.
- W4200422124 isParatext "false" @default.
- W4200422124 isRetracted "false" @default.
- W4200422124 workType "article" @default.