Study of the mammalian G1 regulatory mechanism unifying Rb and p53 pathways.

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We studied the regulatory mechanism of G1 progression of the mammalian cell cycle by focusing on how the COP9 signalosome complex regulates Rb and p53 pathways. We found that the fifth subunit of the COP9 signalosome(CSN5), through interaction with a histone methyltransferase, SMYD3, bound to the promoter region of the p16 gene and regulated its transcription, indicating that the signaling pathway consisting of CSN5, SMYD3, p16, cyclin D-Cdk4/6, and Rb plays an important role in regulation of the hematopoietic somatic stem cells. We also found that the third component, CSN3, participated in the regulation of the COP1-p53 pathway through MLF1.