Richard M. Schultz, Ph.D.
Professor

Ph.D., Chemistry, Brandeis University


Enzymatic modification of histones and the regulation of gene expression

 

The peptidyl cis-trans proline isomerase (PPIase) Cyp33 is a member of the MLL complex that regulates HOX gene expressions. Translocations in the MLL gene lead to acute lymphoblastic leukemias (ALL) and acute myeloid leukemias (AML). In collaboration with Dr. Manuel Diaz, I am interested in determining whether histone modifications are regulated by PPIases such as Cyp33. Proline peptide bonds, as opposed to the peptide bonds of other amino acids, have a near equal probability of having either a cis or trans configuration around their peptide bond. Prolines are present in the sequence of histone proteins near lysines, arginines, and serines/threonines, and the action of acetylases, deacetylases, methylases, de-methylases, kinases, and phosphatases on these histone amino acids may be regulated by PPIases that catalyze the interconversion of the conformation of the nearby proline peptide bond in the histone proteins.

Selected Publications

Janulis, M., Silberman, S., Ambegaokar, A., Gutkind, J.S., and Schultz, R.M., Role of the Mitogen-Activated Protein Kinases and c-Jun/AP-1 trans-Activating Activity in the Regulation of Protease mRNAs and the Malignant Phenotype in NIH 3T3 Fibroblasts, J. Biol. Chem 274, 801-813, 1999

Qi, X., Borowicz1, S., Pramanik, R. Schultz, R.M., Han, J., and Chen, G., Estrogen receptor inhibits c-Jun-dependent stress-induced cell death by binding and modifying c-Jun activity in human breast cancer cells, J. Biol. Chem. 279, 6769-6777, 2004.

Qi, X., Tang, J., Pramanik, R., Schultz, R.M., Shirasawa, S., Sasazuki, T., Han, J., and Chen, G., p38 MAPK activation selectively induces cell death in K-ras mutated human colon cancer cells through regulation of vitamin D receptor, J. Biol. Chem, 279, 22138-22144, 2004.

Schultz, R.M., Cell Cycle, "Apoptosis and Cancer" in Textbook of Biochemistry with Clinical Correlations, 6th Ed., (T. Devlin, ed.), New York, John Wiley and Sons, in press, 2005.


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