Richard H. Goodman
M.D., Ph.D., University of Pennsylvania, 1976
Professor and Director, Vollum Institute
Joint Professor, Cell and Developmental Biology
Joint Professor, Biochemistry and Molecular Biology
Vice-chairman, Medicine
A central problem in neuronal plasticity is determining how recurring synaptic events relate to long-term changes in gene expression. Second messenger systems, particularly those involving cyclic AMP and calcium, are believed to contribute importantly to this signaling process. In many instances, the nuclear target for second messenger signals is a DNA element known as the CRE (cyclic AMP-responsive enhancer). This element allows binding of transcription factors that can, in turn, be activated by cyclic AMP-, calcium-, and growth factor-dependent protein kinases. Control of CRE-containing promoters by the transcription factor CREB has become a paradigm for studies of second messenger-regulated gene expression.
The Goodman laboratory is currently directing its efforts toward answering two questions: how does phosphorylation of CREB lead to gene activation and how is information from distinct signaling pathways integrated to provide a coherent signal to a gene promoter? The laboratory is addressing both questions by examining the function of a nuclear protein, CBP, that binds specifically to the cyclic AMP-activated form of CREB. CBP interacts with a variety of other transcriptional activators, protooncogene products, and general transcription factors in addition to CREB, suggesting that it may serve as a transcriptional "organizer." Thus, it is possible that CBP may allow multiple signaling pathways to converge in a manner that prevents overwhelming the promoter with conflicting information. CBP function is also influenced by several viral transforming proteins and Goodman's group is using these proteins to investigate the role of CBP in transcriptional signaling. Other efforts in the laboratory utilize biophysical approaches to examine the mechanisms underlying CREB-mediated transcriptional activation.
- Goodman, R.H. and Smolik S. CBP/p300 in cell growth, transformation, and development. Genes and Development 14:1553-1577, 2000.
- Craig, J.C., Schumacher, M.A., Mansoor, S.E., Farrens, D.C., Brennan, R.G., and Goodman, R.H. Consensus and variant cAMP-regulated enhancers have distinct CREB binding properties. J. Biol. Chem. 276: 11719-11753, 2001.
- Vo, N, Fjeld, C., and Goodman, R.H. Acetylation of nuclear hormone receptor interacting protein RIP140 regulates binding of the transcriptional corepressor CtBP. Mol. Cell. Biol. (in press).