ACTIVATION OF THE RETINOBLASTOMA GENE-EXPRESSION BY BCL-3 - IMPLICATION FOR MUSCLE-CELL DIFFERENTIATION

The retinoblastoma (Rb) protein is a master regulator of cell cycle. A ccumulating evidence suggests that elevation of Rb expression is a key event in differentiation of various cell types. However the mechanism of regulation of Rb expression is poorly understood. Here we report t hat the candidate oncoprotein Bcl-3, previously characterized as a mem ber of the I kappa B family, activates transcription of the Rb gene, w hose promoter has no typical kappa B sites. A target element for Bcl-3 that matches the consensus for the E4TF1/GABP transcription factor wa s identified. Bcl-3 was shown to promote tetramer formation of E4TF1. During muscle cell differentiation, increased bcl-3 expression was obs erved before the induction of the Rb mRNA. Transient expression of Bcl -3 in myoblasts was shown to induce expression of the endogenous Rb. F urthermore, expression of the antisense bcl-3 RNA in myoblasts suppres sed induction of Rb and myogenic differentiation. These results sugges t that Bcl-3 is an upstream regulator of Rb expression during differen tiation of muscle cells.