Abstract
Myc is a key regulator of cell growth, differentiation and apoptosis, and affects cell fate decisions by activating as well as by inhibiting the expression of cellular genes. Myc is a member of the basic region–helix–loop–helix–leucine zipper (b-HLH-Zip) class of transcription factors, which heterodimerizes with the Max protein and recognizes a consensus Myc binding motif. Stimulation of gene expression by Myc is thought to be mediated by direct binding of Myc–Max heterodimers to specific target genes. So far, only a few genes have been identified as direct binding targets of Myc, raising the possibility that Myc affects gene expression also by indirect mechanisms. In this work we present evidence that v-Myc encoded by the avian retrovirus MC29 stimulates activating transcription factor 2 (ATF2)-dependent transcription. Analysis of the effect of Myc on ATF2 shows that v-Myc prolongs the half-life of ATF2 and induces the phosphorylation of N-terminal sites of ATF2 (Thr-69 and Thr-71) which have previously been identified as the target sites of stress-activated protein kinases and implicated in the regulation of ATF2 activity. Taken together, our results suggest that v-Myc can affect gene expression indirectly by modulating the activity of ATF2.
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Acknowledgements
We thank K Bister, D Crouch, R Davis, D Eick, M Green and J Sedivy for plasmids, antibodies and cells. This work was supported by a grant from the DFG (KL461/8-1) and by the Fonds der chemischen Industrie.
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Miethe, J., Schwartz, C., Wottrich, K. et al. Crosstalk between Myc and activating transcription factor 2 (ATF2): Myc prolongs the half-life and induces phosphorylation of ATF2. Oncogene 20, 8116–8124 (2001). https://doi.org/10.1038/sj.onc.1204966
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DOI: https://doi.org/10.1038/sj.onc.1204966
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