Abstract
THE transcription factor CREB binds to a DNA element known as the cAMP-regulated enhancer (CRE)1–5. CREB is activated through phosphorylation by protein kinase A (PKA)6, but precisely how phosphorylation stimulates CREB function is unknown. One model is that phosphorylation may allow the recruitment of coactivators which then interact with basal transcription factors. We have previously identified a nuclear protein of Mr 265K, CBP, that binds specifically to the PKA-phosphorylated form of CREB7. We have used fluorescence anisotropy measurements to define the equi-librium binding parameters of the phosphoCREB:CBP interaction and report here that CBP can activate transcription through a region in its carboxy terminus. The activation domain of CBP interacts with the basal transcription factor TFIIB through a domain that is conserved in the yeast coactivator ADA-1 (ref. 8). Consistent with its role as a coactivator, CBP augments the activ-ity of phosphorylated CREB to activate transcription of cAMP-responsive genes.
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References
Hoeffler, J. P., Meyer, T. E., Yun, Y., Jameson, J. L. & Habener, J. F. Science 242, 1428–1432 (1988).
Gonzalez, G. A. et al. Nature 337, 749–752 (1989).
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).
Short, J. M., Wynshaw-Boris, A., Short, H. P. & Hanson, R. W. J. biol. Chem. 261, 9721–9726 (1986).
Comb, M., Birnberg, N. C., Seasholtz, A., Herbert, E. & Goodman, H. M. Nature 323, 353–356 (1986).
Gonzalez, G. A. & Montminy, M. R. Cell 59, 675–680 (1989).
Chrivia, J. C. et al. Nature 365, 855–859 (1993).
Berger, S. L. et al. Cell 70, 251–265 (1992).
Heyduk, T. & Lee, J. C. Proc. natn. Acad. Sci. U.S.A. 87, 1744–1748 (1990).
LeTilly, V. & Royer, C. A. Biochemistry 32, 7753–7758 (1993).
Heyduk, T. et al. Nature 364, 548–549 (1993).
Williams, J. S., Dixon, J. E. & Andrisani, O. M. DNA Cell Biol. 12, 183–190 (1993).
Dwarki, V. S., Montminy, M. R. & Verma, I. M. EMBO J. 9, 225–232 (1990).
Loriaux, M. M., Rehfuss, R. P., Brennan, R. G. & Goodman, R. H. Proc. natn. Acad. Sci. U.S.A. 90, 9046–9050 (1993).
Gonzalez, G. A. & Montminy, M. R. Cell 59, 675–680 (1989).
Roberts, S. G. E., Ha, I., Maldonado, E., Reinburg, D. & Green, M. R. Nature 363, 741–744 (1993).
Goodrich, J. A., Hoey, T., Thut, C. J., Admon, C. J., Admon, A. & Tjian, R. Cell 75, 519–530 (1993).
Ferrari, K., Gill, G. & Montminy, M. R. Proc. natn. Acad. Sci. U.S.A. 91, 1210–1213 (1994).
Guan, K. L. & Dixon, J. E. Analyt. Biochem. 192, 262–267 (1991).
Lillie, J. W. & Green, M. R. Nature 338, 39–44 (1989).
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Kwok, R., Lundblad, J., Chrivia, J. et al. Nuclear protein CBP is a coactivator for the transcription factor CREB. Nature 370, 223–226 (1994). https://doi.org/10.1038/370223a0
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DOI: https://doi.org/10.1038/370223a0
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