CELL-CYCLE - REGULATORY EVENTS IN G(1)-]S TRANSITION OF MAMMALIAN-CELLS

A cell divides into two daughter cells by progressing serially through the precisely controlled G1, S, G2, and M phases of the cell cycle. T he crossing of the G1/S border, which is marked by the initiation of D NA synthesis, represents commitment to division into two complete cell s. Beyond this critical point no further external signals are required . We now have more comprehensive knowledge of the temporal sequence of systems at this key transition from G1 to S-growth factor responses, a cascade of kinase reactions, activation of cyclins and their associa ted kinases, and oncogene and tumor suppressor gene products. Furtherm ore, we know that the absolute requirement for calcium and the timing of events associated with calmodulin and the 68 kDa calmodulin-binding protein are consistent with overall Ca++/calmodulin control of all st eps from the response to growth factors in G1 to DNA replication in S phase. We now have to sort out the inter-relationships of myriad contr ol proteins and their relation to the Ca++/calmodulin-dependent contro ls-Which are causes? Which are effects? And which are parallel process es? The answers will be important, as they represent both a much deepe r understanding of this key process of life and an important opportuni ty for improving therapeutic medicine. (C) 1994 Wiley-Liss, Inc.