Function of the D Type Cyclins

Progress of the cycle in Gi phase is controlled in particular by the cyclins of type D and E and by inhibitors of the CDKs (review Morgan, 1995 Pines, 1995 Sherr, 1995). 

Cyclins of type D are of particular importance in control of Gi phase. Of the three cyclins of type D (Dl, D2, D3), two (D2 and D3) do not occur in all cell types, whilst cyclin D1 has a central function in regulation of Gi phase in all cell types. 

Binding partners of the D type cyclins include CDK4 and CDK6 in particular, and CDK4 activation is attributed a key role. For full activation of CDK4, activating phos- 

Cyclin E also performs its function in Gi/S phase. It demonstrates a periodic concentration change with a maximal value at the start of S phase. Afterwards, its concentration falls off sharply within S phase. The gene for cyclin E is also induced by transcription factor E2F which explains the increase in cyclin E at the Gi/S transition. Cyclin E binds and activates CDK2. The activated CDK2 complex is also involved in phosphorylation of the pRb protein. As a consequence, a signal is transmitted, with cooperation of cyclin D, in the direction of the transcription of genes that are essential for the continuation of the cell cycle. 

Negative regulation of the cell cycle in Gi phase is performed in particular by the inhibitors p21 p27 and pl5 , which are activated by external signals (see above, Fig. 13.10). The inhibitor pl6 also regulates by binding free D type cyclin, which leads to destabilization of cyclin D. 

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