Interaction of c-Myc with the pRb-related protein p107 results in inhibition of c-Myc-mediated transactivation.

The product of the c-myc proto-oncogene, c-Myc, is a sequence-specific DNA binding protein with an N-terminal transactivation domain and a C-terminal DNA binding domain. Several lines of evidence indicate that c-Myc activity is essential for normal cell cycle progression. Since the abundance of c-Myc during the cell cycle is constant, ...
c-Myc's activity may be regulated at a post-translational level. We have shown previously that the N-terminus of c-Myc can form a specific complex with the product of the retinoblastoma gene, pRb, in vitro. These data suggested a model in which pRb, or pRb-related proteins, regulate c-Myc activity through direct binding. We show here that the pRb-related protein p107, but not pRb itself, forms a specific complex with the N-terminal transactivation domain of c-Myc in vivo. Binding of p107 to c-Myc causes a significant inhibition of c-Myc transactivation. Expression of c-Myc releases cells from a p107-induced growth arrest, but not from pRb-induced growth arrest. Our data suggest that p107 can control c-Myc activity through direct binding to the transactivation domain and that c-Myc is a target for p107-mediated growth suppression.
Mesh Terms:
Binding Sites, Carrier Proteins, Cell Cycle Proteins, Cell Division, DNA-Binding Proteins, Down-Regulation, E2F Transcription Factors, Humans, Nuclear Proteins, Protein Binding, Proteins, Proto-Oncogene Proteins c-myc, Retinoblastoma-Binding Protein 1, Retinoblastoma-Like Protein p107, Transcription Factor DP1, Transcription Factors, Transcriptional Activation, Tumor Cells, Cultured
EMBO J.
Date: Sep. 01, 1994
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