The human retinoblastoma susceptibility gene promoter is positively autoregulated by its own product

• Published in: The Journal of biological chemistry 1994-02, Vol.269 (8), p.6083-6088
• Main Authors: KEUNCHIL PARK, CHOE, J, OSIFCHIN, N. E, TEMPLETON, D. J, ROBBINS, P. D, SEONG-JIN KIM
• Format: Article
• Language: English
• Subjects: Activating Transcription Factors; Animals; ATF protein; Base Sequence; binding; Binding Sites; Biological and medical sciences; Blood Proteins - metabolism; Cell Line; DNA; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation; gene regulation; genes; Genes, Retinoblastoma; Humans; man; Mink; Molecular and cellular biology; Molecular genetics; Molecular Sequence Data; Neoplasm Proteins - metabolism; Promoter Regions, Genetic; promoters; Rb gene; Rb-1 gene; retinoblastoma; Retinoblastoma Protein - genetics; Retinoblastoma Protein - metabolism; sites; Transcription Factors - metabolism; Transcription, Genetic; Transcription. Transcription factor. Splicing. Rna processing; Tumor Cells, Cultured; tumor suppressor genes
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/S0021-9258(17)37572-5

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.