Induction of S phase by G1 regulatory factors.

The first gap phase (G1) in the mammalian cell cycle plays a pivotal role in determining whether or not cells are to initiate DNA replication. Progression through G1 phase and transition into S phase are positively and negatively regulated by a series of factors, collectively termed G1 regulators. Among them, D-type G1 cyclins and a Cdk inhibitor, p27Kip1, function as the target of growth factors to integrate extracellular signals into cell cycle regulators. Another G1 cyclin, cyclin E, and a transcription factor E2F are situated the furthest downstream of known G1 regulators and seem to be directly involved in the initiation of chromosomal DNA replication. Alterations in G1 regulator genes are often present in human tumors, indicating that G1 regulators participate in tumor suppressive mechanisms as well as in cell proliferation.