Abstract
THE 265K nuclear protein CBP was initially identified as a co-activator for the protein kinase A (PKA)-phosphorylated form of the transcription factor CREB1. The domains in CBP that are involved in CREB binding and transcriptional activation are highly related to the adenoviral ElA-associated cellular protein p300 (refs 2, 3), and to two hypothetical proteins from Caenorhabditis elegans, R10E11.1 and K03H1.10 (refs 4 and 5, respectively), whose functions are unknown. Here, we show that CBP and p300 have similar binding affinity for the PKA-phosphorylated form of CREB, and that p300 can substitute for CBP in potentiating CREB-activated gene expression. We find that E1A binds to CBP through a domain conserved with p300 and represses the CREB-dependent co-activator functions of both CBP and p300. Our results indicate that the gene repression and cell immortalization functions associated with El A involve the inactivation of a family of related proteins that normally participate in second-messenger-regulated gene expression.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Chrivia, J. C. et al. Nature 365, 855–859 (1993).
Eckner, R. et al. Genes Dev. 8, 869–884 (1994).
Arany, Z. et al. Cell 77, 799–800 (1994).
Wilson, R. et al. Nature 368, 32–38 (1994).
Smith, M. & Ainscough, R. Genbank Accession No. Z29560 (1994).
Kwok, R. P. S. et al. Nature 370, 223–226 (1994).
Heyduk, T. et al. Nature 364, 548–549 (1993).
Harlow, E., Franza, B. R. & Schely, C. J. Virol. 55, 533–546 (1985).
Harlow, E., Whyte, P., Franza, B. R. & Schely, C. Molec. cell. Biol. 6, 1579–1589 (1986).
Wang, H.-G.H. et al. J. Virology 67, 476–488 (1993).
Kalvakolanu, D. V. R., Liu, J., Hanson, R. W., Harter, M. L. & Sen, G. C. J. biol. Chem. 267, 2530–2536 (1992).
van Dam, H. et al. Molec. cell. Biol. 10, 5857–5864 (1990).
Arias, J. et al. Nature, 370, 226–229 (1994).
Simon, M. C. et al. Cell 52, 723–729 (1988).
Kraus, V. B., Moran, E. & Nevins, J. R. Molec. cell. Biol. 12, 4391–4399 (1992).
Lee, W. S., Kao, C. C., Bryant, G. O., Liu, X. & Berk, A. J. Cell 67, 365–376 (1991).
Altschul, S. F., Gish, W., Miller, W., Myers, E. W. & Lipman, D. J. J. molec. Biol. 215, 403–410 (1990).
Guan, K. L. & Dixon, J. E. Analyt. Biochem. 192, 262–267 (1991).
Montminy, M. R., Sevarino, K. A., Wagner, J. A., Mandel, G. & Goodman, R. H. Proc. natn. Acad. Sci. U.S.A. 83, 6682–6686 (1986).
Banerjee, A. C. et al. Oncogene 9, 1733–1737 (1994).
Wang, D.-M., Dalie, B. & Harter, M. L. Protein Expr. Pur. 3, 8–17 (1992).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Lundblad, J., Kwok, R., Laurance, M. et al. Adenoviral ElA-associated protein p300 as a functional homologue of the transcriptional co-activator CBP. Nature 374, 85–88 (1995). https://doi.org/10.1038/374085a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/374085a0
This article is cited by
-
MicroRNA-494-3p inhibits formation of fast oxidative muscle fibres by targeting E1A-binding protein p300 in human-induced pluripotent stem cells
Scientific Reports (2021)
-
Update and Potential Opportunities in CBP [Cyclic Adenosine Monophosphate (cAMP) Response Element-Binding Protein (CREB)-Binding Protein] Research Using Computational Techniques
The Protein Journal (2021)
-
Rubinstein-Taybi syndrome in a Saudi boy with distinct features and variants in both the CREBBP and EP300 genes: a case report
BMC Medical Genetics (2019)
-
EP300 single nucleotide polymorphism rs20551 correlates with prolonged overall survival in diffuse large B cell lymphoma patients treated with R-CHOP
Cancer Cell International (2017)
-
Molecular Basis for the Regulation of Transcriptional Coactivator p300 in Myogenic Differentiation
Scientific Reports (2015)
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.