Molecular and functional characterization of the interaction between c-Myc and the MCM helicase

Abstract

The Myc genes (c-myc, n-myc, l-myc, s-myc) encode a family of protein that share structural an biological features and are conserved across all Metazoans. c-Myc, the most extensively studied of his family, has been found deregulated, at different level, in almost every kind of tumor. Originally described as a weak transcriptional activator, further studies disclosed uncommon features for an oncogene or a classic transcription factor. c-Myc exerts his influence on the cell growth, cell cycle progression, apoptosis, but the mechanisms that underlie these functions are still not well understood. In order to shed light on its role as master regulator of cell fate, we isolated the protein complex containing c-Myc. Among the molecular partners associated with c-Myc that were not described before, we have found Mcm7 and Mcm5. Mcm7 and Mcm5 are members of the MCM complex, a ring-shape structure composed by six proteins (Mcm2-7). They play a key role in DNA replication and are recently substituting the traditional tumor marker in clinical diagnosis. We have characterized the interaction between c-Myc and the entire MCM complex. Our studies seem to discard the possibility of a functional meaning of this interaction in c-Myc-mediated transcriptional activation, supporting the hypothesis of a direct effect of c-Myc in replication, already suggested by other authors.