G1 control in yeast and animal cells.

In yeast G1, cyclins control the Cdc28 protein kinase in order to regulate the primary cell cycle gating event known as START. Environmental and internal signals that control the cell cycle do so, apparently, by controlling the synthesis and/or stability of G1 cyclins, hence controlling the activity of the Cdc28 kinase. The substrates of the Cdc28 kinase that are critical for passage through START are not known. One simple hypothesis is that the G1 kinase phosphorylates and thus activates a transcription factor required for the initiation of S phase. The synthesis of an origin of replication-binding factor might be regulated in this fashion. Recent evidence suggests that Cdc28 protein kinase activity directly regulates the transcription of a family of genes whose products are required for DNA replication (N. Marini and S. Reed, in prep.). However, it is not yet known whether this transcriptional activation constitutes the execution of START. The situation in animal cells is more complex. A number of new cyclins and p34s have been identified. It is not clear yet which of these, if any, have functions in G1 and if they do, what functions these might be. If G1 cyclins and p34 kinases do have critical G1 roles, by analogy with yeast, they may couple signals mediated by both positive and negative growth factors to cell cycle progression. Candidates for the critical G1 substrates of these putative G1 protein kinases are the tumor suppressors such as the RB (retinoblastoma) gene product (p105RB).(ABSTRACT TRUNCATED AT 250 WORDS)