Conservative regulation of DNA replication and transcription in mammalian cells

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C-MYC is making complex with a variety of proteins to play numerous roles. We have identified and cloned cDNAs encoding MYC-binding proteins.1) MSSP MSSP was found as an DNA binding protein on origin/enhancer in c-myc gene. MSSP plays a role as DNA replication and transcription factor. MSSP binds to N-terminal portion of C-MYC via its C-terminus portion.2) AMY-1 Using two hybrid system we cloned a novel cDNA encoding AMY-1. AMY-1 was located in the nucleus, and bound to N-terminal region of C-MYC via its C-terminus. AMY-1 acted as a transcription factor and stimulated transcriptional activity of C-MYC.AMY-1 also stimulated C-MYC's transforming activity dramatically.3) Pim-1 Pim-1 was known to transform cells with c-myc. Here we found that Pim-1 was directly associated with C-MYC.Pim-1 induced apoptosis by its overexpression. Signal transduction from Pim-1 to C-MYC may contribute apoptosis pathway.4) DNA polymerase a and cdk2 C-MYC and MSSP were also bound to N-terminal portion of catalytic subunit of DNA polymerase a and cdk2, a protein for G1/S checkpoint protein. MSSP stimulated polymerase activity. These results indicated that MSSP/C-MYC play a key role G1/S,especially the initiation of DNA replication.