Marc Montminy
e-mail: montminy@salk.edu |
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CREB and cyclic AMP responsive transcription
The hormonal stimulation of a variety of eukaryotic genes is mediated by cAMP through a conserved cAMP response element (CRE). The ultimate goal of our laboratory is to characterize the structure and dynamic regulation of nuclear factors which stimulate gene expression in response to this second messenger. Towards this end, we have recently purified and isolated cDNA clones for a transcription factor, CREB, which binds to the CRE and stimulates transcription of cAMP-responsive genes. The phosphorylation of CREB by cAMP-dependent protein kinase is critical to its ability to transactivate genes. Using an in vitro mutagenesis approach, we are currently exploring the mechanism by which phosphorylation trans forms the CREB protein into a fully active transcrip tion factor.
Gonzalez, G.A., Yamamoto, K.K., Fischer, W.H., Karr, D., Menzel, P., Biggs III, W., Vale, W.W., and Montminy, M.R. (1989). A cluster of phosphorylation sites on the cyclic AMP -regulated nuclear factor CREB predicted by its sequence. Nature, 337:749-752.
Hagiwara, M., Brindle, P., Alberta, A., Meinkoth, J, Feramisco, J., Deng T., Karin, M., Shenolikar, S., Montminy, M.R. (1992) Transcriptional attenuation following cAMP induction requires PP-1 mediated dephosphorylation of CREB. Cell, 70:105-113.
Chrivia, J.C., Kwok, R.P.S., Lamb, N., Hagiwara, M., Montminy M.R., and Goodman, R.H. (1993) Phosphorylated CREB binds specifically to the nuclear protein CBP. Nature 365:855-859
Arias, J., Alberts, A.S., Brindle, P., Claret, F.X., Smeal, T., Karin, M., Feramisco, J., and Montminy, M. (1994) Activation of cAMP and mitogen responsive genes relies on a common nuclear factor. Nature 370:226-229
