RDF/XMLNTriplesTurtleShow queryShare
SubjectPredicateObject
http://purl.uniprot.org/citations/16835227http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/16835227http://www.w3.org/2000/01/rdf-schema#comment"Chk2 is a kinase critical for DNA damage-induced apoptosis and is considered a tumor suppressor. Chk2 is essential for p53 transcriptional and apoptotic activities. Although mutations of p53 are present in more than half of all tumors, mutations of Chk2 in cancers are rare, suggesting that Chk2 may be inactivated by unknown alternative mechanisms. Here we elucidate one such alternative mechanism regulated by PML (promyelocytic leukemia) that is involved in acute promyelocytic leukemia (APL). Although p53-inactivating mutations are extremely rare in APL, t(15;17) chromosomal translocation which fuses retinoic acid receptor (RARalpha) to PML is almost always present in APL, while the other PML allele is intact. We demonstrate that PML interacts with Chk2 and activates Chk2 by mediating its autophosphorylation step, an essential step for Chk2 activity that occurs after phosphorylation by the upstream kinase ATM (ataxia telangiectasia-mutated). PML/RARalpha in APL suppresses Chk2 by dominantly inhibiting the auto-phosphorylation step, but inactivation of PML/RARalpha with alltrans retinoic acid (ATRA) restores Chk2 autophosphorylation and activity. Thus, by fusing PML with RARalpha, the APL cells appear to have achieved functional suppression of Chk2 compromising the Chk2-p53 apoptotic pathway."xsd:string
http://purl.uniprot.org/citations/16835227http://purl.org/dc/terms/identifier"doi:10.1074/jbc.m604391200"xsd:string
http://purl.uniprot.org/citations/16835227http://purl.uniprot.org/core/author"Yang S."xsd:string
http://purl.uniprot.org/citations/16835227http://purl.uniprot.org/core/author"Lee C.H."xsd:string
http://purl.uniprot.org/citations/16835227http://purl.uniprot.org/core/author"Brown A.L."xsd:string
http://purl.uniprot.org/citations/16835227http://purl.uniprot.org/core/author"Chung J.H."xsd:string
http://purl.uniprot.org/citations/16835227http://purl.uniprot.org/core/author"Kim M.K."xsd:string
http://purl.uniprot.org/citations/16835227http://purl.uniprot.org/core/author"Pandolfi P.P."xsd:string
http://purl.uniprot.org/citations/16835227http://purl.uniprot.org/core/author"Jeong J.H."xsd:string
http://purl.uniprot.org/citations/16835227http://purl.uniprot.org/core/date"2006"xsd:gYear
http://purl.uniprot.org/citations/16835227http://purl.uniprot.org/core/name"J Biol Chem"xsd:string
http://purl.uniprot.org/citations/16835227http://purl.uniprot.org/core/pages"26645-26654"xsd:string
http://purl.uniprot.org/citations/16835227http://purl.uniprot.org/core/title"Promyelocytic leukemia activates Chk2 by mediating Chk2 autophosphorylation."xsd:string
http://purl.uniprot.org/citations/16835227http://purl.uniprot.org/core/volume"281"xsd:string
http://purl.uniprot.org/citations/16835227http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/16835227
http://purl.uniprot.org/citations/16835227http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/16835227
http://purl.uniprot.org/uniprot/#_A0A068EW80-mappedCitation-16835227http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/16835227
http://purl.uniprot.org/uniprot/#_A0A4V1ES41-mappedCitation-16835227http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/16835227
http://purl.uniprot.org/uniprot/#_A0A4P8PR71-mappedCitation-16835227http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/16835227
http://purl.uniprot.org/uniprot/#_A8JZZ5-mappedCitation-16835227http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/16835227
http://purl.uniprot.org/uniprot/#_D3Z3A6-mappedCitation-16835227http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/16835227
http://purl.uniprot.org/uniprot/#_Q8BSJ6-mappedCitation-16835227http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/16835227
http://purl.uniprot.org/uniprot/#_Q683Z8-mappedCitation-16835227http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/16835227
http://purl.uniprot.org/uniprot/#_O96017-mappedCitation-16835227http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/16835227