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Sequence-specific transcriptional activation by Myc and repression by Max.

Ben May Institute, University of Chicago, Illinois 60637.

ABSTRACT

The c-Myc oncoprotein, which is required for cellular proliferation, resembles in its structure a growing number of transcription factors. However, the mechanism of its action in vivo is not yet clear. The discovery of the specific cognate DNA-binding site for Myc and its specific heterodimerization partner, Max, enabled the use of direct experiments to elucidate how Myc functions in vivo and how this function is modulated by Max. Here we demonstrate that exogenously expressed Myc is capable of activating transcription in vivo through its specific DNA-binding site. Moreover, transcriptional activation by Myc is dependent on the basic region, the integrity of the helix-loop-helix and leucine zipper dimerization motifs located in the carboxy-terminal portion of the protein, and the regions in the amino terminus conserved among Myc family proteins. In contrast to Myc, exogenously expressed Max elicited transcriptional repression and blocked transcriptional activation by Myc through the same DNA-binding site. Our results suggest a functional antagonism between Myc and Max which is mediated by their relative levels in the cells. A model for the activity of Myc and Max in vivo is presented.

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• Barrera-Hernandez, G., Cultraro, C. M., Pianetti, S., Segal, S. (2000). Mad1 Function Is Regulated through Elements within the Carboxy Terminus. Mol. Cell. Biol. 20: 4253-4264 [Abstract] [Full Text]  
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• Bahram, F., Wu, S., Oberg, F., Luscher, B., Larsson, L.-G. (1999). Posttranslational Regulation of Myc Function in Response to Phorbol Ester/Interferon-gamma -Induced Differentiation of v-Myc-Transformed U-937 Monoblasts. Blood 93: 3900-3912 [Abstract] [Full Text]  
• Dang, C. V. (1999). c-Myc Target Genes Involved in Cell Growth, Apoptosis, and Metabolism. Mol. Cell. Biol. 19: 1-11 [Full Text]  
• Zeng, Y., Tang, C.-M., Yao, Y.-L., Yang, W.-M., Seto, E. (1998). Cloning and Characterization of the Mouse Histone Deacetylase-2 Gene. J. Biol. Chem. 273: 28921-28930 [Abstract] [Full Text]  
• Flinn, E. M., Busch, C. M. C., Wright, A. P. H. (1998). myc Boxes, Which Are Conserved in myc Family Proteins, Are Signals for Protein Degradation via the Proteasome. Mol. Cell. Biol. 18: 5961-5969 [Abstract] [Full Text]  
• Sommer, A., Bousset, K., Kremmer, E., Austen, M., Luscher, B. (1998). Identification and Characterization of Specific DNA-binding Complexes Containing Members of the Myc/Max/Mad Network of Transcriptional Regulators. J. Biol. Chem. 273: 6632-6642 [Abstract] [Full Text]  
• Rothermel, B. A., Thornton, J. L., Butow, R. A. (1997). Rtg3p, a Basic Helix-Loop-Helix/Leucine Zipper Protein that Functions in Mitochondrial-induced Changes in Gene Expression, Contains Independent Activation Domains. J. Biol. Chem. 272: 19801-19807 [Abstract] [Full Text]  
• Zhang, H., Fan, S., Prochownik, E. V. (1997). Distinct Roles for MAX Protein Isoforms in Proliferation and Apoptosis. J. Biol. Chem. 272: 17416-17424 [Abstract] [Full Text]  
• Hurlin, P J, Queva, C, Eisenman, R N (1997). Mnt, a novel Max-interacting protein is coexpressed with Myc in proliferating cells and mediates repression at Myc binding sites.. Genes Dev. 11: 44-58 [Abstract]  
• Goetz, T. L., Lloyd, T. L., Griswold, M. D. (1996). Role of E Box and Initiator Region in the Expression of the Rat Follicle-stimulating Hormone Receptor. J. Biol. Chem. 271: 33317-33324 [Abstract] [Full Text]  
• Gallant, P., Shiio, Y., Cheng, P. F., Parkhurst, S. M., Eisenman, R. N. (1996). Myc and Max Homologs in Drosophila. Science 274: 1523-1527 [Abstract] [Full Text]  
• Thompson, A., Zhang, Y., Kamen, D., Jackson, C. W., Cardiff, R. D., Ravid, K. (1996). Deregulated Expression of c-myc in Megakaryocytes of Transgenic Mice Increases Megakaryopoiesis and Decreases Polyploidization. J. Biol. Chem. 271: 22976-22982 [Abstract] [Full Text]  
• Desbarats, L, Gaubatz, S, Eilers, M (1996). Discrimination between different E-box-binding proteins at an endogenous target gene of c-myc.. Genes Dev. 10: 447-460 [Abstract]  
• Wagner, A J, Kokontis, J M, Hay, N (1994). Myc-mediated apoptosis requires wild-type p53 in a manner independent of cell cycle arrest and the ability of p53 to induce p21waf1/cip1.. Genes Dev. 8: 2817-2830 [Abstract]  
• Ayer, D E, Eisenman, R N (1993). A switch from Myc:Max to Mad:Max heterocomplexes accompanies monocyte/macrophage differentiation.. Genes Dev. 7: 2110-2119 [Abstract]  
• Gartel, A. L., Ye, X., Goufman, E., Shianov, P., Hay, N., Najmabadi, F., Tyner, A. L. (2001). Myc represses the p21(WAF1/CIP1) promoter and interacts with Sp1/Sp3. Proc. Natl. Acad. Sci. USA 98: 4510-4515 [Abstract] [Full Text]