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Apoptosis, Senescence, and Cancer pp 223–241Cite as

Interactions Between Myc- and Cyclin-Dependent Kinase Inhibitors in Cancer

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Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

summary

Deregulated cell growth and the inhibition of apoptosis are hallmarks of cancer. The MYC family of oncogenes are pivotal players in tumorigenesis and are altered in most tumor types. c-Myc is the founding member of a family of structurally related basic helix-loop-helix-leucine zipper (bHLH-Zip) proteins that function as sequence-specific transcription factors and are aberrantly expressed in most cancers c-Myc is a key regulator of cell proliferation and differentiation, and its expression is both necessary and sufficient to drive quiescent cells into S phase. Following mitogenic stimulation, c-Myc is rapidly induced; remains elevated throughout the cell cycle and, through dimerization with its bHLH-Zip partner Max, regulates the transcription of genes essential for cell growth and division. Conversely, c-Myc expression is rapidly suppressed by growth inhibitory signals such as transforming growth factor β However, these controls are lost in cancers by translocations, amplifications, and alterations in regulatory signaling pathways, resulting in abnormally high levels of MYC oncoproteins. The precise roles that Myc oncoproteins provide to provoke tumorigenesis are not fully resolved but do include the regulation of target genes that control cell division, differentiation, cell size, and angiogenenesis. These target genes include members of the cyclin dependent kinase inhibitors (encompassing the Ink4 family and the Cip/Kip family of inhibitors), responsible for inhibiting the activity of cyclin/cyclin-dependent kinase complexes that regulate cell cycle traverse. The regulation of these inhibitors by Myc clearly represents an important target in cancer prevention and therapeutics.

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Authors
  1. Kirsteen H. Maclean PhD
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  2. John L. Cleveland PhD
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Editors and Affiliations

  1. Department of Pharmacology and Toxicology and Massey Cancer Center, Virginia Commonwealth University, Richmond, VA

    David A. Gewirtz

  2. Departments of Medicine, Pharmacology and Toxicology, Biochemistry and Massey Cancer Center, Virginia Commonwealth, Richmond, VA

    Shawn E. Holt

  3. Departments of Pathology, Human Genetics, Pharmacology and Toxicology, Biochemistry and Massey Cancer Center, Virginia Commonwealth, Richmond, VA

    Steven Grant

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Maclean, K.H., Cleveland, J.L. (2007). Interactions Between Myc- and Cyclin-Dependent Kinase Inhibitors in Cancer. In: Gewirtz, D.A., Holt, S.E., Grant, S. (eds) Apoptosis, Senescence, and Cancer. Cancer Drug Discovery and Development. Humana Press. https://doi.org/10.1007/978-1-59745-221-2_12

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