Gene-target recognition among members of the Myc superfamily and implications for oncogenesis


Myc and Mad family proteins regulate multiple biological processes through their capacity to influence gene expression directly. Here we show that the basic regions of Myc and Mad proteins are not functionally equivalent in oncogenesis, have separable E-box–binding activities and engage both common and distinct gene targets. Our data support the view that the opposing biological actions of Myc and Mxi1 extend beyond reciprocal regulation of common gene targets. Identification of differentially regulated gene targets provides a framework for understanding the mechanism through which the Myc superfamily governs the growth, proliferation and survival of normal and neoplastic cells.

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Figure 1: Comparison of the basic regions of Myc superfamily members.
Figure 2: c-Myc and Mxi1 basic regions are not equivalent in transformation.
Figure 3: Specific residues in the Myc basic region determine biological activity.
Figure 4: Interaction of Myc and Mxi1 basic regions with DNA.
Figure 5: c-Myc and c-Myc(Mxi1-BR) differ in their capacity to induce apoptosis under high serum conditions.

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We thank H. Land for the CAT reporter constructs; S. Lowe for the mouse ecotropic receptor; S. Hann for the pBabe-c-MycER plasmid; J. Chiorini for the eIF2ß reporter; Y. Jiang and J.K. Lee for technical assistance; and members of the DePinho laboratory for helpful comments. R.C.O. is a recipient of a fellowship from the Jane Coffin Childs Memorial Fund for Medical Research. N.S.-A. is a recipient of a Special Fellowship from the Leukemia Society of America. R.A.D. is supported by grants (RO1HD28317, RO1EY09300) from the National Institutes of Health and is an American Cancer Society Research Professor. Support from the DFCI Cancer Core grant to R.A.D. is acknowledged.

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Correspondence to Ronald A. DePinho.

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O'Hagan, R., Schreiber-Agus, N., Chen, K. et al. Gene-target recognition among members of the Myc superfamily and implications for oncogenesis. Nat Genet 24, 113–119 (2000) doi:10.1038/72761

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