Molecular mechanism of cell proliferation and appoptosis by the actions of transcription/replication factors in mammalian cells.

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We have identified several proteins that interact with C-MYC.These were classified to 4 group ; factor for DNA replication (MSSP), for transcription (AMY-1, MM-1. CBF), for cell-cycle control (p21), and for apoptosis induction (Pim-1). Of the proteins, MSSP futrher interacts with DNA polymerase alpha and PCNA directly, and cdk2 indirectly. C-MYC interacts with PCNA-binding region of p21 to rescue the inhibition of DNA replication by p21. A novel protein AMY-1 interacts the N-terrninal, so called transactivation domain of C-MYC,to stimulate transcriptional activity of C-MYC.AMY-1 was translocated from cytoplasm to nucleus after G1/S transition. Pim-1 is serine/threonine kinase and its target protein was identified, PAP-1. Pim-1 also phosphorylates CDC25 whose gene is known to be a transcriptional targer of C-MYC.These results suggest that a versatile functions of C-MYC occur by a distinguished protein complex during cell cycle.