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Cell Cycle Regulatory Proteins as Targets of Oncogenic Events

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Genomic Instability and Immortality in Cancer

Part of the book series: Pezcoller Foundation Symposia ((PFSO,volume 8))

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Abstract

Many years have passed since the fundamental discoveries of Paul Nurse and Lee Hartwell described the characteristic phenotypes of yeast cell division mutants and the isolation of the first cell cycle regulatory genes (Hartwell et al., 1974; Nurse, 1975). Using very different approaches a large number of investigations have now allowed us to understand how the molecular engine that drives a cell through the division cycle works. At the core of the system are a family of serine/threonine kinases, the cyclin-dependent kinases (Cdks) whose periodic activation leads to the initiation of each cell cycle transition. Their name stems from the fact that they require an associated protein subunit, a cyclin (Evans et al., 1983; Rosenthal et al., 1983) for activity. This biochemical mechanism has been well conserved throughout the evolution, but while in yeast a single Cdk regulates cell cycle progression upon association with distinct cyclins, in higher eukaryotes a family of structurally related proteins exists, each responsible for triggering a certain transition in the division cycle. The various Cdks can associate with different cyclin subunits and form complexes that are activated at distinct times in the cell cycle. In mammals, during the G1 phase, two major protein complexes are activated, the cyclin D and cyclin E associated kinases, while cyclin A complexes are functional throughout S-phase and G2 and cyclin B/Cdc2 is activated at the G2/M-phase transition (see review by Morgan, 1995).

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  1. Department of Experimental Oncology, European Institute of Oncology, 435 Via Ripamonti, 20141, Milan, Italy

    Francesca Fiore & Giulio F. Draetta

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  1. Francesca Fiore
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  2. Giulio F. Draetta
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  1. Roswell Park Cancer Institute, Buffalo, New York, USA

    Enrico Mihich

  2. University of Washington, Seattle, Washington, USA

    Leland Hartwell

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Fiore, F., Draetta, G.F. (1997). Cell Cycle Regulatory Proteins as Targets of Oncogenic Events. In: Mihich, E., Hartwell, L. (eds) Genomic Instability and Immortality in Cancer. Pezcoller Foundation Symposia, vol 8. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-5365-6_17

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