A transcriptional repressor of c-myc

Abstract

In murine plasmacytomas there is deregulated transcription of a translocated c-myc allele and undetectable transcription of the normal, unrearranged c-myc allele. Deregulated c-myc transcription probably contributes to the transformed phenotype of the tumour cells, whereas repression of the normal allele probably reflects the normal turn-off of c-myc in non-dividing plasma cells. We previously identified a plasmacytoma-specific protein which binds to the c-myc promoter region 290 base pairs 5' of the P1 transcription start site. This plasmacytoma repressor factor (myc-PRF; formerly myc-PCF) is not found in cell lines representing earlier B-cell stages during which c-myc is transcribed, so it could be a negative regulator of c-myc transcription in terminally differentiated B cells. Here we report that site-directed deletion of the binding site for this protein leads to a 30-fold increase in transcription of a stably transfected c-myc fusion construct in plasmacytoma cells but has no effect in L cells or 18-81 pre-B cells, which lack the protein. Myc-PRF interacts with another widely distributed protein, myc-CF1 (common factor 1), which binds nearby, and this association may be important in myc-PRF repression.