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Mechanisms of apoptosis by c-Myc

Oncogene volume 18, pages 2967–2987 (1999)Cite this article

Abstract

Much recent research on c-Myc has focused on how it drives apoptosis. c-Myc is widely known as a crucial regulator of cell proliferation in normal and neoplastic cells, but until relatively recently its apoptotic properties, which appear to be intrinsic, were not fully appreciated. Its death-dealing aspects have gained wide attention in part because of their potential therapeutic utility in advanced malignancy, where c-Myc is frequently deregulated and where novel modalities are badly needed. Although its exact function remains obscure, c-Myc is a transcription factor and advances have been made in characterizing target genes which may mediate its apoptotic properties. Candidate regulators and effectors are also emerging. Among recent findings are connections to the CD95/Fas and TNF pathways and roles for the tumor suppressor p19ARF and the c-Myc-interacting adaptor protein Bin1 in mediating cell death. In this review I summarize the data establishing a role for c-Myc in apoptosis in diverse settings and present a modified dual signal model for c-Myc function. It is proposed that c-Myc induces apoptosis through separate `death priming' and `death triggering' mechanisms in which `death priming' and mitogenic signals are coordinated. Investigation of the mechanisms that underlie the triggering steps may offer new therapeutic opportunities.

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Acknowledgements

In preparing this review I relied in part upon comprehensive reviews cited in the text and apologize for the omission of many important original references. Critical reading from members of my laboratory, K Elliott, K Ge, D Sakamuro and M Summers, are gratefully appreciated. Our research is supported by grants from the NIH, the American Cancer Society, the US Army Breast and Prostate Research Programs, Merck and Co., Inc., The Mary Smith Foundation, and The Adler Foundation. GC Prendergast is a Pew Scholar in the Biomedical Sciences.

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Prendergast, G. Mechanisms of apoptosis by c-Myc. Oncogene 18, 2967–2987 (1999). https://doi.org/10.1038/sj.onc.1202727

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