Anna Kashina, Ph.D.

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Associate Professor of Cell and Developmental Biology
Department: Cell and Developmental Biology

Contact information
University of Pennsylvania
School of Veterinary Medicine
Dept. Animal Biology/Biochemistry
3800 Spruce St., Rm. 143 Rosenthal
Philadelphia, PA 19104
Office: 215 746-0895
Fax: 215 573-5189
Graduate Group Affiliations
Education:
BS (Biochemistry)
Moscow State University, 1986.
MS (Biochemistry)
Moscow State University, 1987.
PhD (Cell Biology)
Moscow Institute for Protein Research, 1993.
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Description of Research Expertise

Research Interests
Protein modifications, mouse genetics, cancer, cytoskeleton, cardiovascular development, angiogenesis.

Key words: Protein arginylation, ATE1, arginyltransferase.

Description of Research
Genomes of higher mammals encode an estimated 40,000 proteins, however the complexity of the functions performed by these proteins in vivo is at least an order of magnitude higher. This complexity is achieved in a large part by posttranslational modifications that modulate structure and functions of proteins after synthesis, thus increasing the variety of forms in which the proteins encoded by the same gene can exist in vivo. Evidence suggests that posttranslational modifications constitute a major mechanism for regulation of normal metabolism and disease in higher vertebrates. Discovery and understanding of new posttranslational modifications and uncovering the biological role of the poorly understood modifications constitutes a major emerging field.

The goal of our research is to investigate the physiological role of a previously uncharacterized posttranslational modification, protein arginylation. Knockout of the enzyme responsible for arginylation, ATE1, results embryonic lethality in mice and multiple defects related to heart development and blood vessel remodeling (angiogenesis). Our recent work showed that arginylation regulates many proteins involved in cytoskeleton, cell motility, signaling, and metabolism, and uncovered some mechanisms of this regulation.

Our current studies are focused on three major directions: (1) identification of the ATE1 protein targets and studying the effect of arginylation on their properties and functions; (2) studies of the structure and molecular properties of the mouse ATE1 enzymes; and (3) discovering the mechanisms and pathways that lead to the global physiological effects of protein arginylation.

Lab Personnel:
Reena Rai -- Research Specialist,
Sougata Saha -- Postdoctoral Scholar,
Junling Wang -- Postdoctoral Scholar,
Fangliang Zhang -- Postdoctoral Scholar,
Satoshi Kurosaka -- Postdoctoral Scholar,
Adrian Leu -- Research Specialist,
Li Huang -- Research Specialist.

Selected Publications

Wong,CCL.; XU,T.; Rai,R.; Bailey,A.O.; Yates,J.R.,III; Wolf,Y.I.; Zebroski,H.; Kashina,A.: Global analysis of posttranslational protein arginylation. PLoS Biology 5(10):e258, 2007.

Rai R, Mushegian A, Makarova K, Kashina A: Molecular dissection of arginyltransferases guided by similarity to bacterial peptidoglycan synthases. EMBO Rep 2006 Notes: On line: July 7, 2006.

Kashina,A.S.: Differential arginylation of actin isoforms: the myster of the actin N-terminus. Trends Cell Biology 16: 610-615, 2006 Notes: On line: Oct. 11, 2006.

Karakozova M, Kozak, M, Wong, C. C. L., Bailey, A. O., Yates, J. R, III, Mogilner, A., Zebroski, H., and Kashina, A. : Arginylation of Beta Actin Regulates Actin Cytoskeleton and Cell Motility. Science 2006 Notes: On line: June 22, 2006.

R. Rai and A. Kashina : Identification of mammalian arginyltransferases that modify a specific subset of protein substrates. Proc. Natl. Acad. Sci., USA 102: 10123-10128 2005.

A. Kashina and V. Rodionov : Intracellular Organelle Transport: Few Motors, Many Signals. Trends in Cell Biology 15: 396-398, 2005.

I. Sorokina and A. Kashina : Archived gels as a tool for identification of protein complexes: POLO kinase cofractionates with Drosophila 205 kDa MAP and ncd in mitotic embryonic extracts. Analytical Biochemistry 344: 55-157, 2005.

Kwon YT, Kashina AS,(equal contribution), Davydov IV, Hu RG, An JY, Seo JW, Du F, Varshavsky A.: An essential role of N-terminal arginylation in cardiovascular development. Science 297: 5578-5596, 2002.

Y.T.Kwon, A.S.Kashina, (equal contribution), and A.Varshavsky: Alternative splicing results in differential expression, activity and localization of the two forms of Arginyl-tRNA-Protein transferase, a component of the N-End Rule Pathway. Molecular Cell Biology 19: 182-193, 1999.

A.S.Kashina, G.C.Rogers, and J.M.Scholey: The bimC subfamily of kinesins: essential bipolar mitotic motors driving centrosome separation. Biochem. Biophys. Acta 1357: 257-271, 1997.

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Last updated: 10/03/2012
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