Matches in SemOpenAlex for { <https://semopenalex.org/work/W2537873018> ?p ?o ?g. }
- W2537873018 endingPage "506" @default.
- W2537873018 startingPage "493" @default.
- W2537873018 abstract "MYCN amplification in human cancers predicts poor prognosis and resistance to therapy. However, pharmacological strategies that directly target N-Myc, the protein encoded by MYCN, remain elusive. Here, we identify a molecular mechanism responsible for reciprocal activation between Polo-like kinase-1 (PLK1) and N-Myc. PLK1 specifically binds to the SCFFbw7 ubiquitin ligase, phosphorylates it, and promotes its autopolyubiquitination and proteasomal degradation, counteracting Fbw7-mediated degradation of N-Myc and additional substrates, including cyclin E and Mcl1. Stabilized N-Myc in turn directly activates PLK1 transcription, constituting a positive feedforward regulatory loop that reinforces Myc-regulated oncogenic programs. Inhibitors of PLK1 preferentially induce potent apoptosis of MYCN-amplified tumor cells from neuroblastoma and small cell lung cancer and synergistically potentiate the therapeutic efficacies of Bcl2 antagonists. These findings reveal a PLK1-Fbw7-Myc signaling circuit that underlies tumorigenesis and validate PLK1 inhibitors, alone or with Bcl2 antagonists, as potential effective therapeutics for MYC-overexpressing cancers." @default.
- W2537873018 created "2016-10-28" @default.
- W2537873018 creator A5019839230 @default.
- W2537873018 creator A5020116045 @default.
- W2537873018 creator A5020199656 @default.
- W2537873018 creator A5030928181 @default.
- W2537873018 creator A5031557150 @default.
- W2537873018 creator A5053322275 @default.
- W2537873018 creator A5082799922 @default.
- W2537873018 creator A5083810402 @default.
- W2537873018 creator A5086942958 @default.
- W2537873018 creator A5088189613 @default.
- W2537873018 date "2016-11-01" @default.
- W2537873018 modified "2023-10-18" @default.
- W2537873018 title "Polo-like Kinase-1 Regulates Myc Stabilization and Activates a Feedforward Circuit Promoting Tumor Cell Survival" @default.
- W2537873018 cites W1557877432 @default.
- W2537873018 cites W1963776089 @default.
- W2537873018 cites W1965205650 @default.
- W2537873018 cites W1972166647 @default.
- W2537873018 cites W1974771871 @default.
- W2537873018 cites W1975776530 @default.
- W2537873018 cites W1976874039 @default.
- W2537873018 cites W1995474832 @default.
- W2537873018 cites W1999025078 @default.
- W2537873018 cites W2021536610 @default.
- W2537873018 cites W2022538460 @default.
- W2537873018 cites W2027395744 @default.
- W2537873018 cites W2037874673 @default.
- W2537873018 cites W2039310836 @default.
- W2537873018 cites W2039321774 @default.
- W2537873018 cites W2043586467 @default.
- W2537873018 cites W2044033792 @default.
- W2537873018 cites W2055874017 @default.
- W2537873018 cites W2058654854 @default.
- W2537873018 cites W2059380840 @default.
- W2537873018 cites W2063104773 @default.
- W2537873018 cites W2074305355 @default.
- W2537873018 cites W2076359094 @default.
- W2537873018 cites W2076906857 @default.
- W2537873018 cites W2079760361 @default.
- W2537873018 cites W2091965465 @default.
- W2537873018 cites W2096797981 @default.
- W2537873018 cites W2101124131 @default.
- W2537873018 cites W2102461774 @default.
- W2537873018 cites W2103184621 @default.
- W2537873018 cites W2108541596 @default.
- W2537873018 cites W2109378990 @default.
- W2537873018 cites W2110508238 @default.
- W2537873018 cites W2112357436 @default.
- W2537873018 cites W2112738731 @default.
- W2537873018 cites W2124009292 @default.
- W2537873018 cites W2130925781 @default.
- W2537873018 cites W2138366746 @default.
- W2537873018 cites W2142183096 @default.
- W2537873018 cites W2151962695 @default.
- W2537873018 cites W2161954865 @default.
- W2537873018 cites W2170846478 @default.
- W2537873018 cites W2172242534 @default.
- W2537873018 cites W2254902182 @default.
- W2537873018 cites W2269870164 @default.
- W2537873018 doi "https://doi.org/10.1016/j.molcel.2016.09.016" @default.
- W2537873018 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/27773673" @default.
- W2537873018 hasPublicationYear "2016" @default.
- W2537873018 type Work @default.
- W2537873018 sameAs 2537873018 @default.
- W2537873018 citedByCount "112" @default.
- W2537873018 countsByYear W25378730182017 @default.
- W2537873018 countsByYear W25378730182018 @default.
- W2537873018 countsByYear W25378730182019 @default.
- W2537873018 countsByYear W25378730182020 @default.
- W2537873018 countsByYear W25378730182021 @default.
- W2537873018 countsByYear W25378730182022 @default.
- W2537873018 countsByYear W25378730182023 @default.
- W2537873018 crossrefType "journal-article" @default.
- W2537873018 hasAuthorship W2537873018A5019839230 @default.
- W2537873018 hasAuthorship W2537873018A5020116045 @default.
- W2537873018 hasAuthorship W2537873018A5020199656 @default.
- W2537873018 hasAuthorship W2537873018A5030928181 @default.
- W2537873018 hasAuthorship W2537873018A5031557150 @default.
- W2537873018 hasAuthorship W2537873018A5053322275 @default.
- W2537873018 hasAuthorship W2537873018A5082799922 @default.
- W2537873018 hasAuthorship W2537873018A5083810402 @default.
- W2537873018 hasAuthorship W2537873018A5086942958 @default.
- W2537873018 hasAuthorship W2537873018A5088189613 @default.
- W2537873018 hasBestOaLocation W25378730181 @default.
- W2537873018 hasConcept C104317684 @default.
- W2537873018 hasConcept C121608353 @default.
- W2537873018 hasConcept C134459356 @default.
- W2537873018 hasConcept C146276462 @default.
- W2537873018 hasConcept C1491633281 @default.
- W2537873018 hasConcept C184235292 @default.
- W2537873018 hasConcept C25602115 @default.
- W2537873018 hasConcept C2776715637 @default.
- W2537873018 hasConcept C2777362581 @default.
- W2537873018 hasConcept C29537977 @default.
- W2537873018 hasConcept C502942594 @default.
- W2537873018 hasConcept C54355233 @default.
- W2537873018 hasConcept C555283112 @default.