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Synergistic activation of transcription by CBP and p53

Nature volume 387, pages 819–823 (1997)Cite this article

Abstract

The tumour suppressor p53 is a transcriptional regulator whose ability to inhibit cell growth is dependent upon its transactivation function1,2,3. Here we demonstrate that the transcription factor CBP, which is also implicated in cell proliferation and differentiation4,5,6,7,8,9,10,11,12,13,14, acts as a p53 coactivator and potentiates its transcriptional activity. The amino-terminal activation domain of p53 interacts with the carboxy-terminal portion of the CBP protein both in vitro and in vivo. In transfected SaoS-2 cells, CBP potentiates activation of the mdm-2 gene by p53 and, reciprocally, p53 potentiates activation of a Gal4-responsive target gene by a Gal4(1–147)–CBP(1678–2441) fusion protein. A double point mutation that destroys the transactivation function of p53 also abolishes its binding to CBP and its synergistic function with CBP. The ability of p53 to interact physically and functionally with a co-activator (CBP) that has histone acetyltransferase activity15,16 and with components (TAFs)17,18 of the general transcription machinery indicates that it may have different functions in a multistep activation pathway.

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Figure 1: p53 association with CBP.
Figure 2: p53 association with CBP.
Figure 3: CBP interacts with p53 both in vitro and in vivo.
Figure 4: CBP enhances p53-mediated transactivation.
Figure 5: CBP enhances p53-mediated transactivation.
Figure 6: CBP enhances p53-mediated transactivation.
Figure 7: Synergism between Gal–CBP(1678–2441) and p53.

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Acknowledgements

We thank R. H. Goodman, A. Levine, M. Oren, A. G. Jochemsen, N. C. Jones, A.J.Banister and T. Kouzarides for plasmids; H. Xiao, Y. Tao, L. Wang, S. Stevens and J. D. Fondell for discussions and for critical comments on the manuscript and Y. Nakatani for sharing unpublished observations. This work was supported by a postdoctoral fellowship from Life Science Foundation for Advanced Cancer Studies to W.G., and by grants from the NIH to R.G.R.

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  1. Xiao-Lu Shi

    Present address: HHMI/Pharmacology Department, University of Texas Southwestern Medical Center at Dallas, 5523 Harry Hines Blvd, Texas, 75235-9050, USA

Authors and Affiliations

  1. Laboratory of Biochemistry and Molecular Biology, The Rockefeller University, 1230 York Avenue, New York, 10021, New York, USA

    Wei Gu

  2. Correspondence and requests for materials should be addressed to R.G.R.,

    Robert G. Roeder

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Correspondence to Robert G. Roeder.

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Gu, W., Shi, XL. & Roeder, R. Synergistic activation of transcription by CBP and p53. Nature 387, 819–823 (1997). https://doi.org/10.1038/42972

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