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

Keunchil Park, Jennifer Choe, Nicole E. Osifchin, Dennis J. Templeton, Paul D. Robbins, Seong Jin Kim

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

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-β2 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 autoinducibility may contribute to retinoblastoma.

Original languageEnglish (US)
Pages (from-to)6083-6088
Number of pages6
JournalJournal of Biological Chemistry
Volume269
Issue number8
StatePublished - Feb 25 1994
Externally publishedYes

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