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Critical Reviews™ in Oncogenesis
SJR: 0.631 SNIP: 0.503 CiteScore™: 2.2

ISSN Druckformat: 0893-9675
ISSN Online: 2162-6448

Critical Reviews™ in Oncogenesis

DOI: 10.1615/CritRevOncog.v7.i1-2.80
pages 127-142

Cell Cycle and Cancer: Critical Events at the G1 Restriction Point

Giannino DelSal
Dipartimento di Biochimica Biofisica e Chimica delle Macromolecole V. L. Giorgeri, and Laboratorio Nazionale C.I.B. Area Science Park Padriciano 9934012 Trieste, Italy
Massimo Loda
Department of Pathology, Beth Israel Deaconess Medical Center, West Campus, Harvard Medical School
Michele Pagano
Department of Pathology and Kaplan Comprehensive Cancer Center, New York University, Medical Center MSB 548, 560 First Avenue, New York, NY 10016


In eukaryotic cells, each phase of the cell division cycle is controlled by the sequential activation of various cyclin-dependent kinases (Cdks). These kinases are known to phosphorylate various substrates whose activity is critical for cell cycle progression. As key regulators of the cell cycle, Cdks must be strictly controlled by both extracellular and intracellular signals for adequate responses to occur. There are several distinct molecular mechanisms for controlling the activity of the different Cdks: regulated synthesis and destruction of the activating subunit (cyclin), regulated synthesis and destruction of the inhibitory subunit (Cki), and posttranslational modification of the kinase subunit by highly specific kinases and phosphatases. During the Gl phase of the cell cycle, cells sense, integrate positive and negative signals, and transmit them to the cell cycle machinery. Because of this pivotal role, a vast majority of oncogenic events selectively target elements controlling the Gl. In this review we discuss the elements controlling the G1 phase in relationship to the genesis of cancer.

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