个人简介

B.S., Moscow State University, 1970; Ph.D., Institute of Molecular Biology, 1973. Smits Professor, Caltech, 1992-17; Morgan Professor, 2017-.

研究领域

The ubiquitin system;  the N-end rule pathway;  new approaches to cancer therapy

Biochemistry, Structural, and Molecular Cell Biology; Developmental Biology and Genetics; Microbiology and Immunology; Systems Biology

近期论文

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Turner, G. C. and Varshavsky, A. (2000) Detecting and measuring cotranslational protein degradation in vivo. Science 289, 2117-2120. Xie, Y. and Varshavsky, A. (2000) Physical association of ubiquitin ligases and the 26S proteasome. Proc. Natl. Acad. Sci. USA 97, 2497-2502. Kwon, Y. T., Balogh, S. A., Davydov, I. V., Kashina, A. S., Yoon, J. K., Xie, Y., Gaur, A., Hyde, L., Denenberg, V. H. and Varshavsky, A. (2000) Altered activity, social behavior, and spatial memory in mice lacking the NTAN1p amidase and the asparagine branch of the N-end rule pathway. Mol. Cell. Biol. 20, 4135-4148. Turner, G. C., Du, F. and Varshavsky, A. (2000) Peptides accelerate their uptake by activating a ubiquitin-dependent proteolytic pathway. Nature 405, 579-583. Davydov, I. V. and Varshavsky, A. (2000) RGS4 is arginylated and degraded by the N-end rule pathway in vitro. J. Biol. Chem. 275, 22931-22941. Hershko, A., Ciechanover, A. and Varshavsky, A. (2000) The ubiquitin system. Nature Medicine 6, 1073-1081. Rao, H., Uhlmann, F., Nasmyth, K. and Varshavsky, A. (2001) Degradation of a cohesin subunit by the N-end rule pathway is essential for chromosome stability. Nature 410, 955-960. Xie, Y. and Varshavsky, A. (2001) RPN4 is a ligand, substrate, and transcriptional regulator of the 26S proteasome: a negative feedback circuit. Proc. Natl. Acad. Sci. USA 98, 3056-3061. Kwon, Y. T., Xia, Z.-X., Davydov, I. V., Lecker, S. H. and Varshavsky, A. (2001) Construction and analysis of mouse strains lacking the ubiquitin ligase UBR1 of the N-end rule pathway. Mol. Cell. Biol. 21, 8007-8021. Kwon, Y. T., Kashina, A. S., Davydov, I. V., Hu, R.-G., An, J. Y., Seo, J. W., Du, F. and Varshavsky, A. (2002) An essential role of N-terminal arginylation in cardiovascular development. Science 297, 96-99. Du, F., Navarro-Garcia, F. Xia, Z., Tasaki, T. and Varshavsky, A. (2002) Pairs of dipeptides activate the binding of substrate by ubiquitin ligase through dissociation of its autoinhibitory domain. Proc. Natl. Acad. Sci. USA 99, 14110-14115. Sheng, J., Kumagai, A., Dunphy, W. and Varshavsky, A. (2002) Dissection of c-MOS degron. EMBO J. 21, 6061-6071. Xie, Y. and Varshavsky, A. (2002) The UFD4 ubiquitin ligase lacking the proteasome-binding region catalyzes ubiquitylation but is impaired in proteolysis. Nature Cell Biol. 4, 1003-1007. Varshavsky, A. (2003) The N-end rule and regulation of apoptosis. Nature Cell Biol. 5, 373-376. Kwon, Y. T., Xia, Z., An, J. Y., Tasaki, T., Davydov, I. V., Seo, J. W., Sheng, J., Xie, Y. and Varshavsky, A. (2003) Female lethality and apoptosis of spermatocytes in mice lacking the UBR2 ubiquitin ligase of the N-end rule pathway. Mol. Cell. Biol. 23, 8255-8271. Varshavsky, A. (2004) Spalog and sequelog: neutral terms for spatial and sequence similarity. Curr. Biol. 14, R181-R183. Varshavsky, A. (2005) Regulated protein degradation. Trends Biochem. Sci. 6, 283-286. Tasaki, T., Mulder, L. C. F., Iwamatsu, A., Lee, M. J., Davydov, I. V., Varshavsky, A., Muesing, M. and Kwon, Y. T. (2005) A family of mammalian E3 ubiquitin ligases that contain the UBR motif and recognize N-degrons. Mol. Cell. Biol. 25, 7120-7136. Hu, R.G., Sheng, J., Qi, X., Xu, Z., Takahashi, T. T. and Varshavsky, A. (2005) The N-end rule pathway as a nitric oxide sensor controlling the levels of multiple regulators. Nature 473, 981-986. Zenker, M, Mayerle, J., Lerch, M. M., Tagariello, A., Zerres, K., Durie, P. R., Beier, M., Hülskamp, G., Guzman, C., Rehder, H., Beemer, F. A., Hamel, B., Vanlieferinghen, P., Gershoni-Baruch, R., Vieira, M. W., Dumic, M., Auslender, R., Gil-da-Silva-Lopes, V. L., Steinlicht, S., Rauh, M., Shalev, S. A., Thiel, C., Ekici, A. B., Winterpacht, A., Kwon, Y. T., Varshavsky, A. and Reis, A. (2005) Deficiency of UBR1, a ubiquitin ligase of the N-end rule pathway, causes pancreatic dysfunction, malformations and mental retardation (Johanson-Blizzard syndrome). Nature Genet. 37, 1345-1350. Graciet, E. Hu, R. G., Piatkov, K., Rhee, J. H., Schwarz, E. M. and Varshavsky, A. (2006) Aminoacyl-transferases and the N-end rule pathway of prokaryotic/eukaryotic specificity in a human pathogen. Proc. Natl. Acad. Sci. USA 103, 3078-3083. An, J. Y., Seo, J. W., Tasaki, T., Lee, M. J., Varshavsky, A., Kwon, Y. T. (2006) Impaired neurogenesis and cardiovascular development in mice lacking the E3 ubiquitin ligases UBR1 and UBR2 of the N-end rule pathway. Proc. Natl. Acad. Sci. USA 103, 6212-6217. Varshavsky, A. (2006) The early history of the ubiquitin field. Protein Science 15, 647-654. Hu, R.-G., Brower, C. S., Wang, H., Davydov, I. V, Sheng, J., Zhou, J., Kwon, Y. T. and Varshavsky, A. (2006) Arginyl-transferase, its specificity, putative substrates, bidirectional promoter, and splicing-derived isoforms. J. Biol. Chem. 281, 32559-32573. Tasaki, T., Sohr, R., Hellweg, R., Hortnagl, H., Varshavsky, A. and Kwon, Y. T. (2007) Biochemical and Genetic Studies of UBR3, a Ubiquitin Ligase with a Function in Olfactory and Other Sensory Systems. J. Biol. Chem. 282, 18510-18520.