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A novel function for Myc: inhibition of C/EBP-dependent gene activation
S Mink1, B Mutschler, R Weiskirchen
1Hans Spemann Laboratory, Max Planck for Immunobiology, Freiburg, Germany.
Abstract:
We have investigated the effect of the v-Myc oncoprotein on gene expression in myelomonocytic cells. We find that v-Myc dramatically down-regulates the expression of myelomonocytic-specific genes, such as the chicken mim-1 and lysozyme genes, both of which are known targets for C/EBP transcription factors. We present evidence that Myc downregulates these genes by inhibiting the function of C/EBP transcription factors. Detailed examination of the inhibitory mechanism shows that amino-terminal sequences of v-Myc, but not its DNA-binding domain, are required for the suppression of C/EBP-dependent transactivation. Our findings identify a new function for Myc and reveal a novel mechanism by which Myc affects the expression of other genes.
Insights
The v-Myc oncoprotein suppresses myelomonocytic-specific gene expression by inhibiting C/EBP transcription factors. This novel mechanism involves v-Myc
Area of Science:
- Oncogenic signaling pathways
- Gene regulation in myeloid cells
Background:
- The v-Myc oncoprotein plays a critical role in cellular processes.
- Myelomonocytic-specific genes, including mim-1 and lysozyme, are regulated by C/EBP transcription factors.
Purpose of the Study:
- To investigate the impact of the v-Myc oncoprotein on gene expression in myelomonocytic cells.
- To elucidate the mechanism by which v-Myc influences C/EBP-dependent gene regulation.
Main Methods:
- Analysis of gene expression in myelomonocytic cells.
- Investigation of transcription factor activity and protein domains.
Main Results:
- v-Myc significantly down-regulates myelomonocytic-specific genes (mim-1, lysozyme).
- v-Myc inhibits the function of C/EBP transcription factors.
- Amino-terminal sequences of v-Myc, not the DNA-binding domain, mediate suppression of C/EBP activity.
Conclusions:
- Myc possesses a newly identified function in regulating gene expression.
- A novel inhibitory mechanism of Myc on C/EBP transcription factors has been revealed.