Myc and the cell cycle.

B. Amati, K. Alevizopoulos, J. Vlach

Research output: Contribution to journalArticle

297 Citations (Scopus)

Abstract

Ectopic expression of the c-Myc oncoprotein prevents cell cycle arrest in response to growth-inhibitory signals, differentiation stimuli, or mitogen withdrawal. Moreover, Myc activation in quiescent cells is sufficient to induce cell cycle entry in the absence of growth factors. Thus, Myc transduces a potent mitogenic stimulus but, concomitantly, induces apoptosis in the absence of survival factors. We review here recent progress in our understanding of the molecular mechanisms linking Myc activity to cell cycle control. Myc is a positive regulator of G1-specific cyclin-dependent kinases (CDKs) and, in particular, of cyclin E/CDK2 complexes. Cyclin D/CDK4 and CDK6 may conceivably also be activated by Myc, but the circumstances in which this occurs remain to be explored. Myc acts via at least three distinct pathways which can enhance CDK function: (1) functional inactivation of the CDK inhibitor p27Kip1 and probably also of p21Cip1 and p57Kip2, (2) induction of the CDK-activating phosphatase Cdc25A and (3) - in an ill understood and most likely indirect way - deregulation of cyclin E expression. Constitutive expression of either Myc or cyclin E can prevent growth arrest by p16INK4a (an inhibitor of cyclin D/CDK4, but not of cyclin E/CDK2). In cells, p16INK4a inhibits phosphorylation, and thus induces activation of the Retinoblastoma-family proteins (pRb, p107 and p130). Surprisingly, this effect of p16 is not altered in the presence of Myc or cyclin E. Thus, Myc and cyclin E/CDK2 activity unlink activation of p16 and pRb from growth arrest. Finally, Myc may itself be a functional target of cyclin D/CDK4 through its direct interaction with p107. We discuss how the effects of Myc on cell cycle control may relate to its oncogenic activity, and in particular to its ability to cooperate with activated Ras oncoproteins.

Original languageEnglish
JournalFrontiers in Bioscience
Volume3
Publication statusPublished - 1998

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Cyclin E
Cell Cycle
Cyclin-Dependent Kinases
Cells
Cyclin D
Cell Cycle Checkpoints
Chemical activation
Oncogene Proteins
Growth
cdc25 Phosphatases
CDC2 Protein Kinase
Cyclin-Dependent Kinase 2
Retinoblastoma Protein
Phosphorylation
Deregulation
Mitogens
Intercellular Signaling Peptides and Proteins
Apoptosis
Proteins

Cite this

Amati, B., Alevizopoulos, K., & Vlach, J. (1998). Myc and the cell cycle. Frontiers in Bioscience, 3.

Myc and the cell cycle. / Amati, B.; Alevizopoulos, K.; Vlach, J.

In: Frontiers in Bioscience, Vol. 3, 1998.

Research output: Contribution to journalArticle

Amati, B, Alevizopoulos, K & Vlach, J 1998, 'Myc and the cell cycle.', Frontiers in Bioscience, vol. 3.
Amati B, Alevizopoulos K, Vlach J. Myc and the cell cycle. Frontiers in Bioscience. 1998;3.
Amati, B. ; Alevizopoulos, K. ; Vlach, J. / Myc and the cell cycle. In: Frontiers in Bioscience. 1998 ; Vol. 3.
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