Cell Growth & Differentiation, Vol 3, Issue 9 597-608, Copyright © 1992 by American Association of Cancer Research

ARTICLES

A common set of nuclear factors bind to promoter elements regulated by the retinoblastoma protein

AJ Udvadia, KT Rogers and JM Horowitz
Section of Cell Growth, Regulation and Oncogenesis, Duke University Medical Center, Durham, North Carolina 27710.

A 30-base pair element within the c-fos promoter, termed the RCE (retinoblastoma control element), has previously been shown to be the target of transcriptional regulation by the product of the retinoblastoma (Rb) gene. We have identified three nuclear proteins [retinoblastoma control proteins (RCPs)] that complex with this promoter element in vitro. The Rb gene does not appear to encode the RCPs as the expression of Rb in vivo does not correlate with RCE-RCP complex formation in vitro. A single binding site for the RCPs within the c-fos RCE was identified, and the nucleotides required for protein-DNA complex formation were defined. Similar sequences are found in the promoters of two additional genes that are regulated by Rb (c-myc and TGF-beta 1), and binding assays demonstrate that the RCPs also interact with these elements. Linkage of the c-fos RCE to the herpes simplex virus thymidine kinase promoter led to a 4-fold stimulation of expression in transient transfection assays. Mutations within the RCP binding site that abrogate stable interaction of the RCPs with the RCE in vitro block RCE transcriptional activity in vivo. Our results suggest a role for the RCPs in RCE-dependent transcription and the regulation of transcription by the Rb protein.

This article has been cited by other articles:

				C. Banchio, S. Lingrell, and D. E. Vance Sp-1 Binds Promoter Elements That Are Regulated by Retinoblastoma and Regulate CTP:Phosphocholine Cytidylyltransferase-{alpha} Transcription J. Biol. Chem., May 18, 2007; 282(20): 14827 - 14835. [Abstract] [Full Text] [PDF]

				K. S. Moorefield, S. J. Fry, and J. M. Horowitz Sp2 DNA Binding Activity and trans-Activation Are Negatively Regulated in Mammalian Cells J. Biol. Chem., April 2, 2004; 279(14): 13911 - 13924. [Abstract] [Full Text] [PDF]

				S. B. Kennett, K. S. Moorefield, and J. M. Horowitz Sp3 Represses Gene Expression via the Titration of Promoter-specific Transcription Factors J. Biol. Chem., March 15, 2002; 277(12): 9780 - 9789. [Abstract] [Full Text] [PDF]

				C.-R. YANG, C. WILSON-VAN PATTEN, S. M. PLANCHON, S. M. WUERZBERGER-DAVIS, T. W. DAVIS, S. CUTHILL, S. MIYAMOTO, and D. A. BOOTHMAN Coordinate modulation of Sp1, NF-kappa B, and p53 in confluent human malignant melanoma cells after ionizing radiation FASEB J, February 1, 2000; 14(2): 379 - 390. [Abstract] [Full Text]

				S. B. Kennett, A. J. Udvadia, and J. M. Horowitz Sp3 encodes multiple proteins that differ in their capacity to stimulate or repress transcription Nucleic Acids Res., August 1, 1997; 25(15): 3110 - 3117. [Abstract] [Full Text] [PDF]

				R. S. Cuevo, S. Garrett, and J. M. Horowitz Detection and Functional Characterization of p180, a Novel Cell Cycle Regulated Yeast Transcription Factor That Binds Retinoblastoma Control Elements J. Biol. Chem., February 7, 1997; 272(6): 3813 - 3822. [Abstract] [Full Text] [PDF]