Metastases suppressor NM23-H2 interaction with G-quadruplex DNA within c-MYC promoter nuclease hypersensitive element induces c-MYC expression.
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.
Thakur
Ram Krishna
RK
Proteomics and Structural Biology Unit, Institute of Genomics and Integrative Biology, CSIR, Delhi, India.
Kumar
Praveen
P
Halder
Kangkan
K
Verma
Anjali
A
Kar
Anirban
A
Parent
Jean-Luc
JL
Basundra
Richa
R
Kumar
Akinchan
A
Chowdhury
Shantanu
S
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
D054778:NM23 Nucleoside Diphosphate Kinases; D016271:Proto-Oncogene Proteins c-myc; D004247:DNA; C517940:NME2 protein, human; D003851:Deoxyribonucleases