CELL-CYCLE AND CANCER - CRITICAL EVENTS AT THE G1 RESTRICTION POINT

In eukaryotic cells, each phase of the cell division cycle is controll ed by the sequential activation of various cyclin-dependent kinases (C dks). These kinases are known to phosphorylate various substrates whos e activity is critical for cell cycle progression. As key regulators o f the cell cycle, Cdks must be strictly controlled by both extracellul ar and intracellular signals for adequate responses to occur. There ar e several distinct molecular mechanisms for controlling the activity o f the different Cdks: regulated synthesis and destruction of the activ ating subunit (cyclin), regulated synthesis and destruction of the inh ibitory subunit (Cki), and posttranslational modification of the kinas e subunit by highly specific kinases and phosphatases. During the G1 p hase of the cell cycle, cells sense, integrate positive and negative s ignals, and transmit them to the cell cycle machinery. Because of this pivotal role, a vast majority of oncogenic events selectively target elements controlling the G1. In this review we discuss the elements co ntrolling the G1 phase in relationship to the genesis of cancer.