IFI16 and NM23 bind to a common DNA fragment both in the P53 and the cMYC gene promoters.
In the melanoma M14 cell line, we found that the antimetastatic protein NM23/nucleoside diphosphate kinase binds to the promoters of the oncogene cMYC and of P53, a gene often mutated in human cancer (Cervoni et al. [2006] J. Cell. Biochem. 98:421-428). In a further study, we find now that IFI16, a transcriptional repressor, in both promoters binds to the G-rich fragment that also binds NM23/NDPK. These fragments possess non-B DNA structures. Moreover, by sequential chromatin immunoprecipitation (re-ChIP) we show that the two proteins (IFI16 and NM23/NDPK) are simultaneously bound in vivo to the same DNA fragments. Since P53 stimulates apoptosis and inhibits cellular growth, and cMYC promotes cell growth and, in several instances, also apoptosis, the presence of NM23 and IFI16 on the same DNA fragments suggests their common involvement in the reduced development of some tumors.
Egistelli
Lorenza
L
Dipartimento di Scienze Biochimiche A Rossi Fanelli, Sapienza Università di Roma, Roma, Italy.
Chichiarelli
Silvia
S
Gaucci
Elisa
E
Eufemi
Margherita
M
Schininà
M Eugenia
ME
Giorgi
Alessandra
A
Lascu
Ioan
I
Turano
Carlo
C
Giartosio
Anna
A
Cervoni
Laura
L
D001665:Binding Sites; D045744:Cell Line, Tumor; D004247:DNA / Q000378:metabolism*; D006801:Humans; D008545:Melanoma / Q000473:pathology; D054778:NM23 Nucleoside Diphosphate Kinases / Q000378:metabolism* / Q000502:physiology; D009687:Nuclear Proteins / Q000378:metabolism* / Q000502:physiology; D009838:Oligodeoxyribonucleotides / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism* / Q000502:physiology; D011401:Promoter Regions, Genetic; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*; D012097:Repressor Proteins / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
D054778:NM23 Nucleoside Diphosphate Kinases; D009687:Nuclear Proteins; D009838:Oligodeoxyribonucleotides; D010750:Phosphoproteins; D016271:Proto-Oncogene Proteins c-myc; D012097:Repressor Proteins; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; C076700:IFI16 protein, human; D004247:DNA; C517938:NME1 protein, human