RDF/XMLNTriplesTurtleShow queryShare
SubjectPredicateObject
http://purl.uniprot.org/citations/19043076http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/19043076http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/19043076http://www.w3.org/2000/01/rdf-schema#comment"We previously reported that phosphorylation of topoisomerase (topo) IIalpha at serine-1106 (Ser-1106) regulates enzyme activity and sensitivity to topo II-targeted drugs. In this study we demonstrate that phosphorylation of Ser-1106, which is flanked by acidic amino acids, is regulated in vivo by casein kinase (CK) Idelta and/or CKIepsilon, but not by CKII. The CKI inhibitors, CKI-7 and IC261, reduced Ser-1106 phosphorylation and decreased formation of etoposide-stabilized topo II-DNA cleavable complex. In contrast, the CKII inhibitor, 5,6-dichlorobenzimidazole riboside, did not affect etoposide-stabilized topo II-DNA cleavable complex formation. Since, IC261 specifically targets the Ca(2+)-regulated isozymes, CKIdelta and CKIepsilon, we examined the effect of down-regulating these enzymes on Ser-1106 phosphorylation. Down-regulation of these isozymes with targeted si-RNAs led to hypophosphorylation of the Ser-1106 containing peptide. However, si-RNA-mediated down-regulation of CKIIalpha and alpha' did not alter Ser-1106 phosphorylation. Furthermore, reduced phosphorylation of Ser-1106, observed in HRR25 (CKIdelta/epsilon homologous gene)-deleted Saccharomyces cerevisiae cells transformed with human topo IIalpha, was enhanced following expression of human CKIepsilon. Down-regulation of CKIdelta and CKIepsilon also led to reduced formation of etoposide stabilized topo II-DNA cleavable complex. These results provide strong support for an essential role of CKIdelta/epsilon in phosphorylating Ser-1106 in human topo IIalpha and in regulating enzyme function."xsd:string
http://purl.uniprot.org/citations/19043076http://purl.org/dc/terms/identifier"doi:10.1093/nar/gkn934"xsd:string
http://purl.uniprot.org/citations/19043076http://purl.org/dc/terms/identifier"doi:10.1093/nar/gkn934"xsd:string
http://purl.uniprot.org/citations/19043076http://purl.uniprot.org/core/author"Andersen A.H."xsd:string
http://purl.uniprot.org/citations/19043076http://purl.uniprot.org/core/author"Andersen A.H."xsd:string
http://purl.uniprot.org/citations/19043076http://purl.uniprot.org/core/author"Willard B."xsd:string
http://purl.uniprot.org/citations/19043076http://purl.uniprot.org/core/author"Willard B."xsd:string
http://purl.uniprot.org/citations/19043076http://purl.uniprot.org/core/author"Kinter M."xsd:string
http://purl.uniprot.org/citations/19043076http://purl.uniprot.org/core/author"Kinter M."xsd:string
http://purl.uniprot.org/citations/19043076http://purl.uniprot.org/core/author"Ganapathi M.K."xsd:string
http://purl.uniprot.org/citations/19043076http://purl.uniprot.org/core/author"Ganapathi M.K."xsd:string
http://purl.uniprot.org/citations/19043076http://purl.uniprot.org/core/author"Bukowski R.M."xsd:string
http://purl.uniprot.org/citations/19043076http://purl.uniprot.org/core/author"Bukowski R.M."xsd:string
http://purl.uniprot.org/citations/19043076http://purl.uniprot.org/core/author"Chikamori K."xsd:string
http://purl.uniprot.org/citations/19043076http://purl.uniprot.org/core/author"Chikamori K."xsd:string
http://purl.uniprot.org/citations/19043076http://purl.uniprot.org/core/author"Ganapathi R."xsd:string
http://purl.uniprot.org/citations/19043076http://purl.uniprot.org/core/author"Ganapathi R."xsd:string
http://purl.uniprot.org/citations/19043076http://purl.uniprot.org/core/author"Grabowski D.R."xsd:string
http://purl.uniprot.org/citations/19043076http://purl.uniprot.org/core/author"Grabowski D.R."xsd:string
http://purl.uniprot.org/citations/19043076http://purl.uniprot.org/core/author"Grozav A.G."xsd:string
http://purl.uniprot.org/citations/19043076http://purl.uniprot.org/core/author"Grozav A.G."xsd:string
http://purl.uniprot.org/citations/19043076http://purl.uniprot.org/core/author"Kozuki T."xsd:string
http://purl.uniprot.org/citations/19043076http://purl.uniprot.org/core/author"Kozuki T."xsd:string