A novel form of the RelA nuclear factor kappaB subunit is induced by and forms a complex with the proto-oncogene c-Myc.
Members of both Myc and nuclear factor kappaB (NF-kappaB) families of transcription factors are found overexpressed or inappropriately activated in many forms of human cancer. Furthermore, NF-kappaB can induce c-Myc gene expression, suggesting that the activities of these factors are functionally linked. We have discovered that both c-Myc and v-Myc can induce a previously undescribed, truncated form of the RelA(p65) NF-kappaB subunit, RelA(p37). RelA(p37) encodes the N-terminal DNA binding and dimerization domain of RelA(p65) and would be expected to function as a trans-dominant negative inhibitor of NF-kappaB. Surprisingly, we found that RelA(p37) no longer binds to kappaB elements. This result is explained, however, by the observation that RelA(p37), but not RelA(p65), forms a high-molecular-mass complex with c-Myc. These results demonstrate a previously unknown functional and physical interaction between RelA and c-Myc with many significant implications for our understanding of the role that both proteins play in the molecular events underlying tumourigenesis.
Chapman
Neil R
NR
Division of Gene Expression and Regulation, School of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, UK.
Webster
Gill A
GA
Gillespie
Peter J
PJ
Wilson
Brian J
BJ
Crouch
Dorothy H
DH
Perkins
Neil D
ND
D000595:Amino Acid Sequence; D001665:Binding Sites; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism; D016259:Genes, myc; D006801:Humans; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000235:genetics* / Q000378:metabolism*; D009369:Neoplasms / Q000235:genetics; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D017384:Sequence Deletion; D051996:Transcription Factor RelA; D014162:Transfection
D004268:DNA-Binding Proteins; C000715470:MAS1 protein, human; D016328:NF-kappa B; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc; D011994:Recombinant Proteins; D051996:Transcription Factor RelA