Members of both Myc and nuclear factor κB (NF-κB) families of transcription factors are found overexpressed or inappropriately activated in many forms of human cancer. Furthermore, NF-κB 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-κB 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-κB. Surprisingly, we found that RelA(p37) no longer binds to κB 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.

Abbreviations used: DTT, dithiothreitol; EMSA, electrophoretic mobility-shift assay; MB, Myc box; NF-κB, nuclear factor κB; RHD, Rel homology domain; TNF, tumour necrosis factor; Tos-Lys-CH2Cl, tosyl-lysylchloromethane; Z-VAD-FMK, benzyloxycarbonyl-valylalanyl-dl-aspartylfluoromethane.

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