Homologues
The most studied homologues of cyclin D are found in yeast and viruses.
The yeast homologue of cyclin D, referred to as Cln3, interacts with Cdc28 (cell division control protein) during G1.
In viruses, like Saimiriine herpesvirus 2 (Herpesvirus saimiri) and Human herpesvirus 8 (HHV-8/Kaposi's sarcoma-associated herpesvirus) cyclin D homologues have acquired new functions in order to manipulate the host cell’s metabolism to the viruses’ benefit. Viral cyclin D binds human Cdk6 and inhibits Rb by phosphorylating it, resulting in free transcription factors which result in protein transcription that promotes passage through G1 phase of the cell cycle. Other than Rb, viral cyclin D-Cdk6 complex also targets p27Kip, a Cdk inhibitor of cyclin E and A. In addition, viral cyclin D-Cdk6 is resistant to Cdk inhibitors, such as p21CIP1/WAF1 and p16INK4a which in human cells inhibits Cdk4 by preventing it from forming an active complex with cyclin D.
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