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Thomas Jefferson University - Edward Winter, Ph.D.
Edward Winter, Ph.D.

Biochemistry and Molecular Biology
Thomas Jefferson University
Jefferson Medical College
Department of Biochemistry & Molecular Biology
Associate Professor

Mailing Address
233 South 10th Street, 228 BLSB
Philadelphia, Pennsylvania 19107
United States
Contact Information
Phone: (215) 503-4139
Fax: (215) 503-9162
Edward.Winter@jefferson.edu
Qualifications
Ph.D. (1985) State University of New York at Stony Brook

Expertise and Research Interests
Signal transduction, transcriptional regulation, and meiotic development in yeast.

Reversible phosphorylation of proteins is a major signaling mechanism that regulates development in all eukaryotes. Meiotic development in yeast (sporulation) provides an outstanding model system to study how protein kinase pathways are regulated and how these pathways regulate downstream developmental events. Similar to differentiation programs in higher eukaryotes, induction of sporulation is controlled by a combination of cell-type and environmental signals. Once initiated, a well characterized transcriptional cascade of cell-type specific genes ultimately leads to a cell (or spore) that is genetically and biochemically distinct from its precursor.

This laboratory previously described a mitogen activated protein kinase (MAPK) named SMK1 that is expressed exclusively in meiotic cells where it is required to regulate the differentiation events (spore morphogenesis) that follow meiotic chromosome segregation. Our results show that the SMK1 MAPK plays a central role in regulating multiple steps in spore morphogenesis through distinct downstream targets (Krisak et al., 1994 Genes and Dev., 8:2151, Wagner et al., 1999 Genetics 151:1327). We are presently using molecular-genetic approaches to identify downstream targets of the Smk1 kinase in order to understand how this morphogenetic program is controlled. Molecular-genetic studies from this laboratory have revealed that Smk1 is controlled through a unique signaling pathway that requires the CDK activating kinase Cak1 (Wagner et al., 1997 EMBO J., 16:1305, Schaber et al. 2002, Mol. Cell Biol. 22:57). Cak1 has previously been shown to activate Cdc28, the sole essential CDK in yeast (reviewed in Kaldis et al., 2001). Our studies have demonstrated that Cak1 also activates Ime2, a meiosis-specific cyclin-like kinase that regulates multiple steps in meiotic development. These studies support a model for a meiosis-specific protein kinase signaling network that controls S-phase, chromosome segregation, and spore morphogenesis at multiple self-reinforcing steps (Schaber et al. 2002, Mol. Cell Biol. 22:57, Schindler et al. 2003, Mol. Cell. Biol. 23:66). We are exploring the downstream targets of these pathways which include cell cycle regulators such as the Sic1 cyclin-dependent kinase inhibitor, and transcriptional regulators that include the RSC chromatin remodeling complexes, as well as the Sum1 and Ndt80 sequence-specific DNA binding proteins (Pierce et al. 1998, Mol. Cell. Biol., 18:5970, Xie et al. 1999, EMBO J., 18:6448, Lindgren et al., 2000, EMBO J., 23:6489). In other work we have shown that the Sum1 transcriptional repressor (the key regulator of SMK1 expression) is required for the recombination checkpoint (Lindgren et al., 2000, EMBO J., 23:6489). This checkpoint pathway prevents meiosis when unprocessed recombination intermediates (broken chromosomes) are present thus preventing chromosomal abnormalities in germ cells. This data also provides insight into the role of checkpoint pathways in ordering events in differentiation programs.

Laboratory Staff
Keywords
Biological Sciences; Map Kinase; Meiosis; Microbial Genetics; Sporulation; Yeast
Publications
  • McDonald, C.M., Cooper, K.F., and E. Winter. The Ama1-directed anaphase-promoting complex regulates the Smk1 mitogen-activated protein kinase during meiosis in yeast. Genetics 171(11):901-911, Nov 2005

  • Bungard, D., Reed, M., and E. Winter. RSC1 and RSC2 are required for the expression of mid-late sporulation-specific genes in Saccharomyces cerevisiae. Eukaryotic Cell 3(4):910-918, Aug 2004.

  • Schindler, K., Benjamin, K.S., Martin, A., Boglioli, A., Herskowitz, I., and Winter, E. The Cdk-activating kinase Cak1 promotes meiotic S-phase through Ime2p. Molecular and Cellular Biology 23(23): 8718-8728, Dec 2003

  • Pierce, M., Benjamin, K.R., Montano, S.P., Georgiadis, M., M., Winter, E., and Vershon, A.K. Sum1 and Ndt80 proteins compete for binding to MSE sequences that control meiotic gene expression. Molecular and Cellular Biology 23(14): 4814-4825, July 2003

  • Schaber, M., Lindgren, A., Schindler, K., Bungard, D., Kaldis, P., and E. Winter. Cak1 promotes meiosis and spore formation in Saccharomyces cerevisiae in a Cdc28-independent fashion. Molecular and Cellular Biology 22(23): 57-68, Jan 2002

  • Kaldis, P., Tsakraklides, V., Ross, K., Winter, E., and A. Cheng The CDK-Activating Kinase, edited by Philipp Kaldis, Eurekah Press 2001.

  • Lindgren, A., Bungard, D., Pierce, M., Xie, J., Vershon, A., and Winter, E. (2000) The pachytene checkpoint in Saccharomyces cerevisiae requires the Sum1 transcriptional repressor. The EMBO Journal. 19(23): 6489-6497, Dec 2000

  • Xie J, Pierce M, Gailus-Durner V, Wagner M, Winter E, Vershon AK. Sum1 and Hst1 repress middle sporulation-specific gene expression during mitosis in Saccharomyces cerevisiae. EMBO Journal. 18(22): 6448-54, Nov 1999

  • Wagner M, Briza P, Pierce M, Winter E. Distinct steps in yeast spore morphogenesis require distinct SMK1 MAP kinase thresholds. Genetics. 151(4): 1327-40, Apr 1999

  • Kaldis P, Pitluk ZW, Bany IA, Enke DA, Wagner M, Winter E, Solomon MJ. Localization and regulation of the cdk-activating kinase (Cak1p) from budding yeast. Journal of Cell Science. 111: 3585-96, Dec 1998

  • Pierce M, Wagner M, Xie J, Gailus-Durner V, Six J, Vershon AK, Winter E. Transcriptional regulation of the SMK1 mitogen-activated protein kinase gene during meiotic development in Saccharomyces cerevisiae. Molecular and Cellular Biology. 18(10): 5970-80, Oct 1998

  • Wagner M, Pierce M, Winter E. The CDK-activating kinase CAK1 can dosage suppress sporulation defects of smk1 MAP kinase mutants and is required for spore wall morphogenesis in Saccharomyces cerevisiae. EMBO Journal. 16(6): 1305-17, Mar 1997

  • Hall JP, Cherkasova V, Elion E, Gustin MC, Winter E. The osmoregulatory pathway represses mating pathway activity in Saccharomyces cerevisiae: isolation of a FUS3 mutant that is insensitive to the repression mechanism. Molecular and Cellular Biology. 16(12): 6715-23, Dec 1996

  • Reardon BJ, Gordon D, Ballard MJ, Winter E. DNA binding properties of the Saccharomyces cerevisiae DAT1 gene product. Nucleic Acids Research. 23(23): 4900-6, Dec 1995

  • Krisak L, Strich R, Winters RS, Hall JP, Mallory MJ, Kreitzer D, Tuan RS, Winter E. SMK1, a developmentally regulated MAP kinase, is required for spore wall assembly in Saccharomyces cerevisiae. Genes and Development. 8(18): 2151-61, Sep 1994

  • Reardon BJ, Winters RS, Gordon D, Winter E. A peptide motif that recognizes A.T tracts in DNA. Proceedings of the National Academy of Sciences (USA). 90(23): 11327-31, Dec 1993

  • Brewster JL, de Valoir T, Dwyer ND, Winter E, Gustin MC. An osmosensing signal transduction pathway in yeast. Science. 259(5102): 1760-3, Mar 1993

  • Zhang, S., Lockshin, C., Herbert, A., Winter, E., and Rich A. Zoutin, a Z-DNA binding protein in Saccharomyces cerevisiae. The EMBO Journal, 11,3787-3796, 1992.

  • Ballard, M.J., Tyndall, W.A., Shingle, J.M., Hall, D., and E. Winter. Tyrosine phosphorylation of a yeast 40 kDa protein occurs in response to mating pheromone. The EMBO Journal, 10, 3753-3758, 1991.

  • Winter, E. and Varshavsky, A. A DNA binding protein that recognizes oligo(dA).oligo(dT) tracts. The EMBO Journal 8, 1867-1877, 1989.

  • Kahn, S., Yamamoto, F., Almoguera, C., Winter, E., Forrester, K., Jordano, J. and Perucho, M. The c-K-ras gene and human cancer. Anticancer Research 7, 639-652, 1987.

  • Winter, E. and Perucho, M. Oncogene amplification during tumorogenesis of established rat fibroblasts reversibly transformed by activated human ras oncogenes. Mol. Cell Biol. 6, 2562-2570, 1986.

  • Winter, E., Yamamoto, F., Almoguera, C. and Perucho, M. A method to detect and characterize point mutations in transcribed genes: Amplification and overexpression of the mutant c-Ki-ras allele in human tumor cells. Proc. Natl. Acad. Sci. USA 82, 7575-7579, 1985.

  • Winter, E., Levy, D. and Gordon J.S. Changes in the H-1 histone complement during myogenesis. I. Establishment by differential coupling of H-1 species synthesis to DNA replication. J. Cell Biol. 101, 167-174, 1985.

  • Winter, E., Palatnik, C.M., Williams, D.L., Coles, L.S., Wells, J.R.E. and Gordon, J.S. Changes in the H-1 histone complement during myogenesis. II. Regulation by differential coupling of H-1 variant mRNA accumulation to DNA replication. J. Cell Biol. 101, 175-181, 1985.

Individual Expertise profile of Edward Winter, Ph.D., Copyright © Edward Winter, Ph.D..
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