Sidney Pestka Professor UMDNJ-RWJMS Molecular Genetics & Microbiology 675 Hoes Lane Piscataway. NJ 08854-5635 (732) 235-4567 FAX - 5223 pestka@umdnj.edu

Receptors. signal transduction. interferons and cytokines. protein expression

Cell surface receptors for cytokines and growth factors provide the initial ligand-receptor interactions that begin the cascade of signal transduction events that lead to specific gene expression. The panoply of these components and events are a major focus of this laboratory. Discovery of the components of these receptors and signal pathways requires a broad series of approaches that span many disciplines: molecular biology. microbiology. biochemistry. cell biology and genetics. The use of reverse genetics is used to delineate the specific sites of the functional elements. The combination of molecular biology and genetics proves to be an enormously powerful tool to delineate all these events. The successful use of these procedures will lead to an integral understanding of the detailed molecular events that lead from the cell surface to gene expression. the normal control of these processes in differentiation and development. and the aberration of these processes in diseases such as cancer. The discovery of a novel protein methyltransferase resulted from our studies and is continuing in several directions to provide a unique perspective in these areas.

Selected Publications

Sinsimer KS, Gratacós FM, Knapinska AM, Lu J, Krause CD, Wierzbowski AV, Maher LR, Scrudato S, Rivera YM, Gupta S, Turrin DK, De La Cruz MP, Pestka S, Brewer G. (2008) Chaperone Hsp27, a novel subunit of AUF1 protein complexes, functions in AU-rich element-mediated mRNA decay. Mol Cell Biol. Jun 23. [Epub ahead of print]

Adler V, Bowne W, Michl J, Sookraj KA, Ikram K, Pestka S, Izotova L, Zenilman M, Friedman FK, Qu Y, Pincus MR. (2008) Site-specific phosphorylation of raf in cells containing oncogenic ras-p21 is likely mediated by jun-N-terminal kinase. Ann Clin Lab Sci. 38(1):47-56.

Krause CD, Pestka S. (2007) Historical developments in the research of interferon receptors.
Cytokine Growth Factor Rev. 18(5-6):473-82.

Qu Y, Adler V, Izotova L, Pestka S, Bowne W, Michl J, Boutjdir M, Friedman FK, Pincus MR. (2007) The dual-specificity kinases, TOPK and DYRK1A, are critical for oocyte maturation induced by wild-type--but not by oncogenic--ras-p21 protein. Front Biosci. 12:5089-97.

Pestka S. (2007) The Interferons: 50 years after their discovery there is much more to learn. J Biol Chem. 282(28):20047-51.

Krause CD, Yang ZH, Kim YS, Lee JH, Cook JR, Pestka S. (2007) Protein arginine methyltransferases: evolution and assessment of their pharmacological and therapeutic potential. Pharmacol Ther. 113(1):50-87.

Garcia CS, Curiel RE, Mwatibo JM, Pestka S, Li H, Espinoza-Delgado I.(2006) The antineoplastic agent bryostatin-1 differentially regulates IFN-gamma receptor subunits in monocytic cells: transcriptional and posttranscriptional control of IFN-gamma R2.
J Immunol. 177(4):2707-16.

Qu Y. Adler V. Chu T. Platica O. Michl J. Pestka S. Izotova L. Boutjdir M. Pincus MR. (2006) Two dual specificity kinases are preferentially induced by wild-type rather than by oncogenic RAS-P21 in Xenopus oocytes. Front Biosci. 11:2420-7.

Cook JR. Lee JH. Yang ZH. Krause CD. Herth N. Hoffmann R. Pestka S. (2006) FBXO11/PRMT9. a new protein arginine methyltransferase. symmetrically dimethylates arginine residues. Biochem Biophys Res Commun. 342(2):472-81.

Krause CD. He W. Kotenko S. Pestka S. (2006) Modulation of the activation of Stat1 by the interferon-gamma receptor complex. Cell Res. 16(1):113-23.

Krause CD. Lavnikova N. Xie J. Mei E. Mirochnitchenko OV. Jia Y. Hochstrasser RM. Pestka S. (2006) Preassembly and ligand-induced restructuring of the chains of the IFN-gamma receptor complex: the roles of Jak kinases. Stat1 and the receptor chains. Cell Res. 16(1):55-69.

Desai SD. Haas AL. Wood LM. Tsai YC. Pestka S. Rubin EH. Saleem A. Nur-E-Kamal A. Liu LF. (2006) Elevated expression of ISG15 in tumor cells interferes with the ubiquitin/26S proteasome pathway. Cancer Res. 66(2):921-8.

Krause CD. Mei E. Mirochnitchenko O. Lavnikova N. Xie J. Jia Y. Hochstrasser RM. Pestka S. (2006) Interactions among the components of the interleukin-10 receptor complex. Biochem Biophys Res Commun. 340(2):377-85.

Adler V. Qu Y. Smith SJ. Izotova L. Pestka S. Kung HF. Lin M. Friedman FK. Chie L. Chung D. Boutjdir M. Pincus MR. (2005) Functional interactions of Raf and MEK with Jun-N-terminal kinase (JNK) result in a positive feedback loop on the oncogenic Ras signaling pathway. Biochemistry. 44(32):10784-95.

Krause CD. Pestka S. (2005) Evolution of the Class 2 cytokines and receptors. and discovery of new friends and relatives. Pharmacol Ther. 106(3):299-346.

Wu W. Kerrigan JE. Yadav P. Schwartz B. Izotova L. Lavoie TB. Pestka S. (2004) Design and construction of a phosphorylatable chimeric monoclonal antibody with a highly stable phosphate. Oncol Res. 14(11-12):541-58.

Pestka S. Krause CD. Walter MR. (2004) Interferons. interferon-like cytokines. and their receptors. Immunol Rev. 202:8-32.

Lee JH. Cook JR. Yang ZH. Mirochnitchenko O. Gunderson SI. Felix AM. Herth N. Hoffmann R. Pestka S. (2005) PRMT7. a new protein arginine methyltransferase that synthesizes symmetric dimethylarginine. J Biol Chem. 280(5):3656-64.

Miranda TB. Khusial P. Cook JR. Lee JH. Gunderson SI. Pestka S. Zieve GW. Clarke S. (2004) Spliceosome Sm proteins D1. D3. and B/B' are asymmetrically dimethylated at arginine residues in the nucleus. Biochem Biophys Res Commun. 323(2):382-7.

Logsdon NJ. Jones BC. Allman JC. Izotova L. Schwartz B. Pestka S. Walter MR. (2004) The IL-10R2 binding hot spot on IL-22 is located on the N-terminal helix and is dependent on N-linked glycosylation. J Mol Biol. 342(2):503-14.

Pestka S. Krause CD. Sarkar D. Walter MR. Shi Y. Fisher PB. (2004) Interleukin-10 and related cytokines and receptors. Annu Rev Immunol. 22:929-79.

Kang DC. Gopalkrishnan RV. Lin L. Randolph A. Valerie K. Pestka S. Fisher PB. (2004) Expression analysis and genomic characterization of human melanoma differentiation associated gene-5. mda-5: a novel type I interferon-responsive apoptosis-inducing gene. Oncogene. 23(9):1789-800.

Brewer G. Saccani S. Sarkar S. Lewis A. Pestka S. (2003) Increased interleukin-10 mRNA stability in melanoma cells is associated with decreased levels of A + U-rich element binding factor AUF1. J Interferon Cytokine Res. 23(10):553-64.

Pestka S. (2003) A dance between interferon-alpha/beta and p53 demonstrates collaborations in tumor suppression and antiviral activities. Cancer Cell. 4(2):85-7.

Chie L. Cook JR. Chung D. Hoffmann R. Yang Z. Kim Y. Pestka S. Pincus MR. (2003) A protein methyl transferase. PRMT5. selectively blocks oncogenic ras-p21 mitogenic signal transduction. Ann Clin Lab Sci. 33(2):200-7.

Sauane M. Gopalkrishnan RV. Lebedeva I. Mei MX. Sarkar D. Su ZZ. Kang DC. Dent P. Pestka S. Fisher PB. (2003) Mda-7/IL-24 induces apoptosis of diverse cancer cell lines through AK/STAT-independent pathways. J Cell Physiol. 196(2):334-45.

Sauane M. Gopalkrishnan RV. Sarkar D. Su ZZ. Lebedeva IV. Dent P. Pestka S. Fisher PB. (2003) MDA-7/IL-24: novel cancer growth suppressing and apoptosis inducing cytokine. Cytokine Growth Factor Rev. 14(1):35-51.

Krause CD. Mei E. Xie J. Jia Y. Bopp MA. Hochstrasser RM. Pestka S. (2002) Seeing the light: preassembly and ligand-induced changes of the interferon gamma receptor complex in cells. Mol Cell Proteomics. 1(10):805-15.

Clark WA. Izotova L. Philipova D. Wu W. Lin L. Pestka S. (2002) Site-specific 32P-labeling of cytokines. monoclonal antibodies. and other protein substrates for quantitative assays and therapeutic application. Biotechniques. Suppl:76-8. 80-7.

Fabbrizio E. El Messaoudi S. Polanowska J. Paul C. Cook JR. Lee JH. Negre V. Rousset M. Pestka S. Le Cam A. Sardet C. (2002) Negative regulation of transcription by the type II arginine methyltransferase PRMT5. EMBO Rep. 3(7):641-5.