Retinoblastoma protein expression leads to reduced Oct-1 DNA binding activity and enhances interleukin-8 expression

Tumor cell lines with a defective retinoblastoma gene are unable to transcr ibe the HLA class II genes in response to IFN-gamma treatment, and reconsti tution of functional Rb rescues IFN-gamma-induced class II gene expression. However, the molecular mechanism of Rb rescue of the class II genes is unk nown. We have examined the effect of Rb expression on the activation of the promoter for HLA-DRA, the prototype class II gene. Oct-1, a POU domain tra nscription factor, was identified as a repressor of HLA-DRA promoter activi ty in the Rb-defective cells. Rb expression led to phosphorylation of Oct-1 , thus relieving its repressive effect. Oct-1 has also been shown to repres s interleukin 8 promoter activity. Consistent with reduced levels of Oct-1 DNA binding activity in the Rb-transformed cell lines, interleukin 8 expres sion is higher in these cell lines.