Faculty

Anna Kashina, Ph.D.

faculty photo
Professor of Physiology
Department: Physiology
Graduate Group Affiliations

Contact information
University of Pennsylvania
School of Veterinary Medicine
Department of Biomedical Sciences
3800 Spruce St., Rm. 143 Rosenthal
Philadelphia, PA 19104
Office: 215 746-0895
Fax: 215 573-5189
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

Rassier Dilson E, Kashina Anna: Protein arginylation of cytoskeletal proteins in the muscle: modifications modifying function. [PMID 30789755] American journal of physiology. Cell physiology 316(5): C668-C677, May 2019.

Dhakal Rabin, Tong Chunyi, Anderson Sean, Kashina Anna S, Cooperman Barry, Bau Haim H: Dynamics of intracellular stress-induced tRNA trafficking. [PMID 30496477] Nucleic acids research 47(4): 2002-2010, Feb 2019.

Wang Junling, Pejaver Vikas Rao, Dann Geoffrey P, Wolf Max Y, Kellis Manolis, Huang Yun, Garcia Benjamin A, Radivojac Predrag, Kashina Anna: Target site specificity and in vivo complexity of the mammalian arginylome. [PMID 30385798] Scientific reports 8(1): 16177, Nov 2018.

Pavlyk Iuliia, Leu Nicolae A, Vedula Pavan, Kurosaka Satoshi, Kashina Anna: Rapid and dynamic arginylation of the leading edge β-actin is required for cell migration. [PMID 29384244] Traffic (Copenhagen, Denmark) 19(4): 263-272, 04 2018.

Vedula Pavan, Kashina Anna: The makings of the 'actin code': regulation of actin's biological function at the amino acid and nucleotide level. [PMID 29739859] Journal of cell science 131(9), May 2018.

Rodriguez Alexis, Kashina Anna: Posttranscriptional and Posttranslational Regulation of Actin. [PMID 30312009] Anatomical record (Hoboken, N.J. : 2007) 301(12): 1991-1998, Dec 2018.

Vedula Pavan, Kurosaka Satoshi, Leu Nicolae Adrian, Wolf Yuri I, Shabalina Svetlana A, Wang Junling, Sterling Stephanie, Dong Dawei W, Kashina Anna: Diverse functions of homologous actin isoforms are defined by their nucleotide, rather than their amino acid sequence. [PMID 29244021] eLife 15(6), 12 2017.

Srinivasan Satish, Guha Manti, Kashina Anna, Avadhani Narayan G: Mitochondrial dysfunction and mitochondrial dynamics-The cancer connection. [PMID 28104365] Biochimica et biophysica acta. Bioenergetics 1858(8): 602-614, Aug 2017.

Efimova Nadia, Korobova Farida, Stankewich Michael C, Moberly Andrew H, Stolz Donna B, Wang Junling, Kashina Anna, Ma Minghong, Svitkina Tatyana: βIII Spectrin Is Necessary for Formation of the Constricted Neck of Dendritic Spines and Regulation of Synaptic Activity in Neurons. [PMID 28576936] The Journal of neuroscience : the official journal of the Society for Neuroscience 37(27): 6442-6459, 07 2017.

Wang Junling, Pavlyk Iuliia, Vedula Pavan, Sterling Stephanie, Leu N Adrian, Dong Dawei W, Kashina Anna: Arginyltransferase ATE1 is targeted to the neuronal growth cones and regulates neurite outgrowth during brain development.[PMID 28844905] Developmental biology 430(1): 41-51, 10 2017.

Wang Junling, Han Xuemei, Leu Nicolae Adrian, Sterling Stephanie, Kurosaka Satoshi, Fina Marie, Lee Virginia M, Dong Dawei W, Yates John R, Kashina Anna: Protein arginylation targets alpha synuclein, facilitates normal brain health, and prevents neurodegeneration.[PMID 28900170] Scientific reports 7(1): 11323, 09 2017.

Leite Felipe de Souza, Kashina Anna, Rassier Dilson E: Posttranslational Arginylation Regulates Striated Muscle Function.[PMID 27111480] Exercise and sport sciences reviews 44(3): 98-103, 07 2016.

Leite Felipe S, Minozzo Fábio C, Kalganov Albert, Cornachione Anabelle S, Cheng Yu-Shu, Leu Nicolae A, Han Xuemei, Saripalli Chandra, Yates John R, Granzier Henk, Kashina Anna S, Rassier Dilson E: Reduced passive force in skeletal muscles lacking protein arginylation.[PMID 26511365] American journal of physiology. Cell physiology 310(2): C127-35, Jan 2016.

Rai R, Zhang F, Colavita K, Leu N A, Kurosaka S, Kumar A, Birnbaum M D, Győrffy B, Dong D W, Shtutman M, Kashina A: Arginyltransferase suppresses cell tumorigenic potential and inversely correlates with metastases in human cancers.[PMID 26686093] Oncogene 35(31): 4058-68, 08 2016.

Wang, J., Kashina, A. S.: Assaying ATE1 Activity In Vitro [PMID 26285883] Methods Mol Biol 1337: 73-77, 2015.

Zhang Fangliang, Patel Devang M, Colavita Kristen, Rodionova Irina, Buckley Brian, Scott David A, Kumar Akhilesh, Shabalina Svetlana A, Saha Sougata, Chernov Mikhail, Osterman Andrei L, Kashina Anna: Arginylation regulates purine nucleotide biosynthesis by enhancing the activity of phosphoribosyl pyrophosphate synthase.[PMID 26175007] Nature communications 6: 7517, Jul 2015.

Kashina Anna S: Protein Arginylation: Over 50 Years of Discovery.[PMID 26285874] Methods in molecular biology (Clifton, N.J.) 1337: 1-11, 2015.

Kashina Anna S: Preparation of ATE1 Enzyme from Native Mammalian Tissues. [PMID 26285878] Methods in molecular biology (Clifton, N.J.) 1337: 33-7, 2015.

Kashina Anna S, Yates John R: Analysis of Arginylated Peptides by Subtractive Edman Degradation.[PMID 26285887] Methods in molecular biology (Clifton, N.J.) 1337: 105-7, 2015.

Kashina Anna S: Development of New Tools for the Studies of Protein Arginylation. [PMID 26285890] Methods in molecular biology (Clifton, N.J.) 1337: 139-45, 2015.

Wang, J., Kashina, A. S.: Bacterial Expression and Purification of Recombinant Arginyltransferase (ATE1) and Arg-tRNA Synthetase (RRS) for Arginylation Assays [PMID 26285882] Methods Mol Biol 1337: 67-71, 2015.

Saha, S., Wang, J., Kashina, A. S.: High-Throughput Arginylation Assay in Microplate Format. [PMID 26285884] Methods Mol Biol 1337: 79-82, 2015.

Kashina, A. S., Yates, J. R.: Analysis of Arginylated Peptides by Subtractive Edman Degradation [PMID 26285887] Methods Mol Biol 1337: 105-107, 2015.

Kashina, A. S., Yates, J. R.: Identification of Arginylated Proteins by Mass Spectrometry [PMID 26285886] Methods Mol Biol 1337: 93-104, 2015.

Kashina, A. S.: Assaying ATE1 Activity in Yeast by β-Gal Degradation [PMID 26285881] Methods Mol Biol 1337: 59-65, 2015.

Kashina, A. S.: Development of New Tools for the Studies of Protein Arginylation. [PMID 26285890] Methods Mol Biol 1337: 139-145, 2015.

Kashina, A. S.: Preparation of ATE1 Enzyme from Native Mammalian Tissues[PMID 26285878] Methods Mol Biol 1337: 33-37, 2015.

Kashina, A. S.: Protein Arginylation: Over 50 Years of Discovery [PMID 26285874] Methods Mol Biol 1337: 1-11, 2015.

Zhang, F., Colavita, K., Rodionova, I., Buckley, B., Scott, D., Kumar, A., Shabalina, S., Saha, S., Chernov, M., Osterman, A., Kashina, A. S.: Arginylation regulates purine biosynthesis by facilitating the biological activity of phosphorybosyl pyrophospate synthase. [PMID 26175007] Mol Biol Cell 25, 2014.

Guha M, Srinivasan S, Ruthel G, Kashina A K, Carstens R P, Mendoza A, Khanna C, Van Winkle T, Avadhani N G: Mitochondrial retrograde signaling induces epithelial-mesenchymal transition and generates breast cancer stem cells. [PMID 24186204] Oncogene 33(45): 5238-50, Nov 2014.

Lian Lurong, Suzuki Aae, Hayes Vincent, Saha Sougata, Han Xuemei, Xu Tao, Yates John R, Poncz Mortimer, Kashina Anna, Abrams Charles S: Loss of ATE1-mediated arginylation leads to impaired platelet myosin phosphorylation, clot retraction, and in vivo thrombosis formation. [PMID 24293517] Haematologica 99(3): 554-60, Mar 2014.

Wang, J., Han, X., Wong, C. C. L., Cheng, H., Aslanian, A., Xu, T., Leavis, P., Roder, H., Hedstrom, L., Yates, J. R., Kashina, A.: Arginyltransferase ATE1 catalyzes midchain arginylation of proteins at side chain carboxylates in vivo [PMID 24529990] Chem Biol 21(3): 331-337, 2014.

Lian, L., Suzuki, A., Hayes, V., Saha, S., Han, X., Xu, T., Yates, J. R., Poncz, M., Kashina, A., Abrams, C. S.: Loss of ATE1-mediated arginylation leads to impaired platelet myosin phosphorylation, clot retraction, and in vivo thrombosis formation. [PMID 24293517] Haematologica 99(3): 554-560, 2014.

Kashina, A.: Protein arginylation, a global biological regulator that targets actin cytoskeleton and the muscle [PMID 25125176] Anat Rec (Hoboken) 297(9): 1630-1636, 2014.

Cornachione, A. S., Leite, F. S., Wang, J., Leu, N. A., Kalganov, A., Volgin, D., Han, X., Xu, T., Cheng, Y. S., Yates, J. R. R., Rassier, D. E., Kashina, A.: Arginylation of myosin heavy chain regulates skeletal muscle strength [PMID 25017061] Cell Rep 8(2): 470-476, 2014.

Shabalina, S. A., Spiridonov, N. A., Kashina, A.: Sounds of silence: synonymous nucleotides as a key to biological regulation and complexity. [PMID 23293005] Nucleic Acids Res 41(4): 2073-2094, 2013.

Zhang, F., Saha, S., Shabalina, S. A., Kashina, A.: Differential arginylation of actin isoforms is regulated by coding sequence-dependent degradation [PMID 20847274] Science 329(5998): 1534-1537, 2010.

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Last updated: 07/05/2019
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