CDC6 interacts with c-Myc to inhibit E-box-dependent transcription by abrogating c-Myc/Max complex.

The c-myc oncogene product (c-Myc) is a transcription factor that dimerizes with Max and recognizes the E-box sequence. It plays key functions in cell proliferation, differentiation and apoptosis. It is generally thought that c-Myc transactivates genes encoding proteins essential to cell-cycle progression by binding to the E-boxes that control them. ...
The functions of c-Myc are also thought to be modulated by its associated proteins, several of which have recently been identified. In this study, we found that c-Myc directly bound in vivo and in vitro to the N-terminal region of human CDC6, a component of the pre-replication complex, and that both co-localized in cell nuclei. CDC6 bound to the C-proximal region of c-Myc, thereby competing with Max on the E-box sequence and changing c-Myc/Max heterodimer to a Max/Max homodimer. In consequence, the E-box-dependent transcription activity of c-Myc was abrogated. These results suggest that, in addition to its DNA replication activity, CDC6 also has a role as a transcriptional suppressor of c-Myc.
Mesh Terms:
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, Basic-Leucine Zipper Transcription Factors, Binding, Competitive, Cell Cycle Proteins, DNA-Binding Proteins, Dimerization, Fluorescent Antibody Technique, Indirect, Gene Expression Regulation, Hela Cells, Humans, Mutation, Nuclear Proteins, Protein Binding, Proto-Oncogene Proteins c-myc, Recombinant Fusion Proteins, Repressor Proteins, Response Elements, Transcription Factors, Transcription, Genetic
FEBS Lett.
Date: Jul. 14, 2000
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