title: Metastases suppressor NM23-H2 interaction with G-quadruplex DNA within c-MYC promoter nuclease hypersensitive element induces c-MYC expression.
abstract: Regulatory influence of the G-quadruplex or G4 motif present within the nuclease hypersensitive element (NHE) in the promoter of c-MYC has been noted. On the other hand, association of NM23-H2 to the NHE leads to c-MYC activation. Therefore, NM23-H2 interaction with the G4 motif within the c-MYC NHE presents an interesting mechanistic possibility. Herein, using luciferase reporter assay and chromatin immunoprecipitation we show NM23-H2 mediated c-MYC activation involves NM23-H2-G4 motif binding within the c-MYC NHE. G4 motif complex formation with recombinant NM23-H2 was independently confirmed using fluorescence energy transfer, which also indicated that the G4 motif was resolved to an unfolded state within the protein-bound complex. Taken together, this supports transcriptional role of NM23-H2 via a G4 motif.
authors.affiliation: Proteomics and Structural Biology Unit, Institute of Genomics and Integrative Biology, CSIR, Delhi, India.
authors.forename: Ram Krishna
authors.initials: RK
authors.lastname: Thakur
authors.forename: Praveen
authors.initials: P
authors.lastname: Kumar
authors.forename: Kangkan
authors.initials: K
authors.lastname: Halder
authors.forename: Anjali
authors.initials: A
authors.lastname: Verma
authors.forename: Anirban
authors.initials: A
authors.lastname: Kar
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Parent
authors.forename: Richa
authors.initials: R
authors.lastname: Basundra
authors.forename: Akinchan
authors.initials: A
authors.lastname: Kumar
authors.forename: Shantanu
authors.initials: S
authors.lastname: Chowdhury
mesh_terms: D001665:Binding Sites; D002460:Cell Line; D004247:DNA / Q000737:chemistry*; D003851:Deoxyribonucleases / Q000378:metabolism; D054856:G-Quadruplexes; D016259:Genes, myc; D006801:Humans; D009154:Mutation; D054778:NM23 Nucleoside Diphosphate Kinases / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis; D015533:Transcriptional Activation
chemical_list: D054778:NM23 Nucleoside Diphosphate Kinases; D016271:Proto-Oncogene Proteins c-myc; D004247:DNA; C517940:NME2 protein, human; D003851:Deoxyribonucleases