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CDC6 interacts with c-Myc to inhibit E-box-dependent transcription by abrogating c-Myc/Max complex
M Takayama1, T Taira, S M Iguchi-Ariga
1Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-ku, Sapporo, Japan.
FEBS Letters
|July 19, 2000
Summary
Cellular Myc (c-Myc) protein activity is modulated by CDC6, a DNA replication factor. CDC6 binding to c-Myc inhibits its transcriptional activity by preventing dimerization with Max.
Area of Science:
- Molecular Biology
- Cell Biology
- Oncology
Background:
- The c-Myc oncogene product (c-Myc) is a crucial transcription factor regulating cell proliferation, differentiation, and apoptosis.
- c-Myc typically transactivates target genes by binding to E-box sequences, often in complex with Max.
- The functions of c-Myc are known to be modulated by various associated proteins.
Purpose of the Study:
- To investigate the interaction between c-Myc and CDC6.
- To elucidate the functional consequences of this interaction on c-Myc transcriptional activity.
Main Methods:
- In vivo and in vitro binding assays to confirm direct interaction between c-Myc and CDC6.
- Co-localization studies in cell nuclei.
- Analysis of c-Myc/Max heterodimerization and Max/Max homodimerization.
- Assessment of E-box-dependent transcription activity.
Main Results:
- c-Myc directly binds to the N-terminal region of human CDC6.
- Both c-Myc and CDC6 were found to co-localize within cell nuclei.
- CDC6 binds to the C-proximal region of c-Myc, displacing Max and promoting Max/Max homodimer formation.
- This interaction abrogates c-Myc's E-box-dependent transcription activity.
Conclusions:
- CDC6 interacts directly with c-Myc, modulating its function.
- CDC6 acts as a transcriptional suppressor of c-Myc, independent of its role in DNA replication.
- This finding reveals a novel regulatory mechanism for c-Myc activity.
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