Matches in SemOpenAlex for { <https://semopenalex.org/work/W2994848488> ?p ?o ?g. }
Showing items 1 to 88 of
88
with 100 items per page.
- W2994848488 abstract "The human polo-like kinase PLK1 coordinates mitotic chromosome segregation by phosphorylating multiple chromatin- and kinetochore-binding proteins. How PLK1 activity is directed to specific substrates via phosphopeptide recognition by its carboxyl-terminal polo-box domain (PBD) is poorly understood. Here, we combine molecular, structural and chemical biology to identify a determinant for PLK1 substrate recognition that is essential for proper chromosome segregation. We show that mutations ablating an evolutionarily conserved, Tyr-lined pocket in human PLK1 PBD trigger cellular anomalies in mitotic progression and timing. Tyr pocket mutations selectively impair PLK1 binding to the kinetochore phosphoprotein substrate PBIP1, but not to the centrosomal substrate NEDD1. Through a structure-guided approach, we develop a small-molecule inhibitor, Polotyrin, which occupies the Tyr pocket. Polotyrin recapitulates the mitotic defects caused by mutations in the Tyr pocket, further evidencing its essential function, and exemplifying a new approach for selective PLK1 inhibition. Thus, our findings support a model wherein substrate discrimination via the Tyr pocket in the human PLK1 PBD regulates mitotic chromosome segregation to preserve genome integrity." @default.
- W2994848488 created "2019-12-26" @default.
- W2994848488 creator A5000950100 @default.
- W2994848488 creator A5013834674 @default.
- W2994848488 creator A5025128576 @default.
- W2994848488 creator A5026575963 @default.
- W2994848488 creator A5031167105 @default.
- W2994848488 creator A5044641487 @default.
- W2994848488 creator A5051936081 @default.
- W2994848488 creator A5057292937 @default.
- W2994848488 creator A5058680543 @default.
- W2994848488 creator A5069032762 @default.
- W2994848488 creator A5075346091 @default.
- W2994848488 creator A5080498381 @default.
- W2994848488 date "2019-11-04" @default.
- W2994848488 modified "2023-09-23" @default.
- W2994848488 title "A cryptic hydrophobic pocket in the polo-box domain of the polo-like kinase PLK1 regulates substrate recognition and mitotic chromosome segregation." @default.
- W2994848488 doi "https://doi.org/10.17863/cam.46689" @default.
- W2994848488 hasPublicationYear "2019" @default.
- W2994848488 type Work @default.
- W2994848488 sameAs 2994848488 @default.
- W2994848488 citedByCount "0" @default.
- W2994848488 crossrefType "journal-article" @default.
- W2994848488 hasAuthorship W2994848488A5000950100 @default.
- W2994848488 hasAuthorship W2994848488A5013834674 @default.
- W2994848488 hasAuthorship W2994848488A5025128576 @default.
- W2994848488 hasAuthorship W2994848488A5026575963 @default.
- W2994848488 hasAuthorship W2994848488A5031167105 @default.
- W2994848488 hasAuthorship W2994848488A5044641487 @default.
- W2994848488 hasAuthorship W2994848488A5051936081 @default.
- W2994848488 hasAuthorship W2994848488A5057292937 @default.
- W2994848488 hasAuthorship W2994848488A5058680543 @default.
- W2994848488 hasAuthorship W2994848488A5069032762 @default.
- W2994848488 hasAuthorship W2994848488A5075346091 @default.
- W2994848488 hasAuthorship W2994848488A5080498381 @default.
- W2994848488 hasConcept C104317684 @default.
- W2994848488 hasConcept C146276462 @default.
- W2994848488 hasConcept C192838845 @default.
- W2994848488 hasConcept C2778354886 @default.
- W2994848488 hasConcept C29537977 @default.
- W2994848488 hasConcept C30481170 @default.
- W2994848488 hasConcept C54355233 @default.
- W2994848488 hasConcept C552990157 @default.
- W2994848488 hasConcept C83640560 @default.
- W2994848488 hasConcept C84815855 @default.
- W2994848488 hasConcept C86803240 @default.
- W2994848488 hasConcept C93304396 @default.
- W2994848488 hasConcept C95444343 @default.
- W2994848488 hasConceptScore W2994848488C104317684 @default.
- W2994848488 hasConceptScore W2994848488C146276462 @default.
- W2994848488 hasConceptScore W2994848488C192838845 @default.
- W2994848488 hasConceptScore W2994848488C2778354886 @default.
- W2994848488 hasConceptScore W2994848488C29537977 @default.
- W2994848488 hasConceptScore W2994848488C30481170 @default.
- W2994848488 hasConceptScore W2994848488C54355233 @default.
- W2994848488 hasConceptScore W2994848488C552990157 @default.
- W2994848488 hasConceptScore W2994848488C83640560 @default.
- W2994848488 hasConceptScore W2994848488C84815855 @default.
- W2994848488 hasConceptScore W2994848488C86803240 @default.
- W2994848488 hasConceptScore W2994848488C93304396 @default.
- W2994848488 hasConceptScore W2994848488C95444343 @default.
- W2994848488 hasLocation W29948484881 @default.
- W2994848488 hasOpenAccess W2994848488 @default.
- W2994848488 hasPrimaryLocation W29948484881 @default.
- W2994848488 hasRelatedWork W1899781694 @default.
- W2994848488 hasRelatedWork W1980220988 @default.
- W2994848488 hasRelatedWork W1981316821 @default.
- W2994848488 hasRelatedWork W1985622227 @default.
- W2994848488 hasRelatedWork W2015137398 @default.
- W2994848488 hasRelatedWork W2025004309 @default.
- W2994848488 hasRelatedWork W2027650871 @default.
- W2994848488 hasRelatedWork W2030690279 @default.
- W2994848488 hasRelatedWork W2041874300 @default.
- W2994848488 hasRelatedWork W2058045779 @default.
- W2994848488 hasRelatedWork W2059128890 @default.
- W2994848488 hasRelatedWork W2069449346 @default.
- W2994848488 hasRelatedWork W2116282691 @default.
- W2994848488 hasRelatedWork W2130478624 @default.
- W2994848488 hasRelatedWork W2146453026 @default.
- W2994848488 hasRelatedWork W2244737621 @default.
- W2994848488 hasRelatedWork W2767686517 @default.
- W2994848488 hasRelatedWork W2969940091 @default.
- W2994848488 hasRelatedWork W3110459767 @default.
- W2994848488 hasRelatedWork W3213734029 @default.
- W2994848488 isParatext "false" @default.
- W2994848488 isRetracted "false" @default.
- W2994848488 magId "2994848488" @default.
- W2994848488 workType "article" @default.