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. Accumulating 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 that the candidate oncoprotein Bcl-3, previously characterized as a member of the IkappaB family, activates transcription of the Rb gene, whose promoter has no typical kappaB sites. A target element for Bcl-3 that matches the consensus for the E4TF1/GABP transcription factor was identified. Bcl-3 was shown to promote tetramer formation of E4TF1. During muscle cell differentiation, increased bcl-3 expression was observed before the induction of the Rb mRNA. Transient expression of Bcl-3 in myoblasts was shown to induce expression of the endogenous Rb. Furthermore, expression of the antisense bcl-3 RNA in myoblasts suppressed induction of Rb and myogenic differentiation. These results suggest that Bcl-3 is an upstream regulator of Rb expression during differentiation of muscle cells.
Shiio
Y
Y
Department of Oncology, The Institute of Medical Science, The University of Tokyo, Japan.
Sawada
J
J
Handa
H
H
Yamamoto
T
T
Inoue
J
J
D000081242:B-Cell Lymphoma 3 Protein; D001483:Base Sequence; D002454:Cell Differentiation / Q000235:genetics; D004247:DNA; D005786:Gene Expression Regulation / Q000502:physiology*; D016161:Genes, Retinoblastoma; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D009132:Muscles / Q000166:cytology*; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors; D014407:Tumor Cells, Cultured
D000081242:B-Cell Lymphoma 3 Protein; C000631344:BCL3 protein, human; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors; D004247:DNA