The human retinoblastoma susceptibility gene promoter is positively autoregulated by its own product.
The product of the retinoblastoma susceptibility gene is a 105-kDa protein that has properties of a cell cycle regulatory factor. Previous reports indicated that two distinct DNA-binding factors, RBF-1 and ATF, play an important part in the transcription of the human retinoblastoma gene (Rb). Recently, we demonstrated that pRb activates expression of the human transforming growth factor-beta 2 gene through ATF-2. Since the human Rb gene promoter also contains an ATF-2-like binding site, we examined whether pRb can regulate its own expression through ATF-2. Here we report that overexpression of Rb stimulates Rb promoter activity through the ATF binding site in a variety of different cell types. Mutation of the ATF binding site of the Rb promoter abolishes the Rb autoinduction. We have also determined that the carboxyl-terminal domain of pRb is responsible for the Rb autoinduction through ATF-2. Rb autoinduction may be important for maintaining the action of pRb during cell growth, and loss of autoinductibility may contribute to retinoblastoma.
Park
K
K
Laboratory of Chemoprevention, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
Choe
J
J
Osifchin
N E
NE
Templeton
D J
DJ
Robbins
P D
PD
Kim
S J
SJ
D051696:Activating Transcription Factors; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D001798:Blood Proteins / Q000378:metabolism; D002460:Cell Line; D004247:DNA; D005786:Gene Expression Regulation; D016161:Genes, Retinoblastoma; D006801:Humans; D008907:Mink; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000378:metabolism; D011401:Promoter Regions, Genetic; D016160:Retinoblastoma Protein / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D051696:Activating Transcription Factors; D001798:Blood Proteins; D009363:Neoplasm Proteins; D016160:Retinoblastoma Protein; D014157:Transcription Factors; D004247:DNA