Joseph P Stein, PhD
Education & Fellowships
- PhD: Harvard University, 1976
Retinoid regulation of gene expression
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Molecular Biology of Retinoic Acid Signal Transduction.
Retinoic acid is an isoprenoid lipid derivative of vitamin A which plays an extremely critical role in the regulation of growth, differentiation, and morphogenesis in vertebrates. All of these effects of retinoic acid are due to selective alterations in the pattern of gene expression in target cells, which is mediated by the binding of the retinoid ligand to two different families of nuclear retinoid receptors. The retinoid receptors activate transcription of target genes by binding as heterodimers to specific response elements located in the promoter region of these genes. Our research program has for some time been focused on the molecular mechanisms by which this transcriptional activation is accomplished. Recently, a new family of cytochrome P450 enzymes (CYP26) was discovered to play a significant role in the biogenesis of active metabolites of retinoic acid. We are attempting to identify and clone all members of this gene family. Their promoters will be characterized in order to determine how retinoic acid regulates their expression. Also, their cDNAs will be expressed in mammalian cells in order to characterize the enzymes kinetically and biochemically, in order to examine the role played by this cytochrome family in the transduction of the retinoid signal.
Yan, Z.H., S. Noonan, L. Nagy, P.J.A Davies and J.P. Stein (1996) Retinoic acid induction of the tissue transglutaminase promoter is mediated by a novel response element. Mol. Cell. Endocrinol., 120:203-212.
Nagy, L., Thomazy, V.A., Saydak, M.M., Stein, J.P. and Davies, P.J.A. (1997) The promoter of the mouse tissue transglutaminase gene directs tissue-specific, retinoid-regulated and apoptosis-linked expression. Cell Death Differ., 4:534-547.
Nagy, L., Saydak, M., Shipley, N., Lu, S., Basilion, J.P., Yan, Z.H., Syka, P., Chandraratna, R.A.S., Stein, J.P., Heyman, R.A. and Davies, P.J.A. (1996) Identification and characterization of a versatile retinoid response element (RARE-RXRE) in the mouse tissue transglutaminase gene promoter. J. Biol. Chem. 271:4355-4365.