Professor of Biology, California Institute of Technology

Investigator, Howard Hughes Medical Institute

 

Division of Biology (156-29), California Institute of Technology

1200 East California Boulevard, Pasadena, California 91125

Telephone: (626) 395-3162 Fax: (626) 395-5739

E-mail: deshaies(at)caltech.edu

Date and Place of Birth

September 25, 1961; Waterbury, Connecticut

Education

1979-1983 Cornell University, Ithaca, New York. B.S. in Biochemistry
1983-1988 University of California, Berkeley. Ph.D. in Biochemistry

Positions

1982-1983 Undergraduate Research Assistant
Project: Reconstitution of protein synthesis in isolated chloroplasts
Research Advisor: Dr. Andre Jagendorf
Department of Plant Physiology, Cornell University, Ithaca, NY

1983-1988 Graduate Research Assistant
Project: Identification of genes required for protein translocation into the yeast endoplasmic reticulum
Research Advisor: Dr. Randy Schekman
Department of Biochemistry, University of California at Berkeley

1988-1990 Postdoctoral Research Associate
Project: Analysis of a component of the yeast protein translocation machinery
Research Advisor: Dr. Randy Schekman
Department of Biochemistry, University of California at Berkeley

1990-1994 Postdoctoral Research Associate
Project: Biochemical dissection of the G1-S cell cycle transition.
Research Advisor: Dr. Marc Kirschner
Department of Biochemistry and Biophysics, University of California at San Francisco

1994-2000 Assistant Professor of Biology
California Institute of Technology
Research Area: Regulation of cell division and ubiquitin-dependent proteolysis

2000-2004 Associate Professor of Biology and Assistant Investigator, HHMI
California Institute of Technology
Research Area: Regulation of cell division and ubiquitin-dependent proteolysis

2005- Professor of Biology and Investigator, HHMI
California Institute of Technology
Research Area: Regulation of cell division and ubiquitin-dependent proteolysis

2006- Executive Officer, Division of Biology, California Institute of Technology

Honors and Awards

1983 Graduated from Cornell University with Honors and Distinction

1984-1985 Regents Fellowship, University of California

1986-1988 NIH Graduate Assistantship

1990-1997 Lucille P. Markey Charitable Trust Scholar Award

1995-1998 Searle Scholar Award

1997-2000 Burroughs-Wellcome New Investigator Award

1997-1999 Beckman Young Investigator Award

1999 ASCB-Promega Early Career Life Scientist Award

2000 Appointed as Assistant Investigator, Howard Hughes Medical Institute

2007 Caltech Graduate Student Council Award for Teaching

2007 Elected as Felow, American Association for the Advancement of Science

2008 Biology Undergraduate Student Advisory Committee Teaching Award

2011 Elected as Fellow, American Academy for Arts and Sciences

 

Professional Activities

Scientific Meeting Organization

1999 Member of Program Committee for 1999 ASCB National Meeting

1999 Member of Program Committee for 2000 ASBMB National Meeting

1999 Co-Chair (with Daniel Klionsky), ASCB mini- symposium on Protein Turnover and Autophagy

2000 Chair, ASBMB symposium: 'Control of cell function by regulated proteolysis'

2001 Co-chair (with Judith Bond), ASBMB Satellite meeting on 'Proteolysis and Cellular Regulation'

2002 Co-organizer (with Jim Roberts), American Association of Cancer Research meeting on 'Ubiquitin'

2003 Co-organizer (with Peter Howley and Mark Hochstrasser), The Ubiquitin Family meeting, Cold Spring Harbor, April 2003

2004 Co-chair (with Avram Hershko), plenary session on Proteasomes in Cancer, 2004 AACR National Meeting

2005 Co-organizer (with Peter Howley and Joan Conaway), The Ubiquitin Family meeting, Cold Spring Harbor, April 2005

2006 Member, Education Program Committee for 2007 AACR National Meeting

2007 Co-organizer (with Joan Conaway and Wade Harper), The Ubiquitin Family meeting, Cold Spring Harbor, April 2007

2007 Chair, plenary session on Ubiquitin in Cancer, 2007 AACR National Meeting

2012 Co-organizer (with Ivan Dikic), Keystone Symposium, Ubiquitin Signaling, Whistler, British Columbia, March 2012

Editorial

1999 Member, Editorial Board, Journal of Cell Biology

1999 Co-editor (with Tyler Jacks), volume on Cell Proliferation, Current Opinion in Cell Biology

2001 Co-editor (with Martin Eilers), volume on Cell Proliferation, Current Opinion in Cell Biology

2001 Founding Associate Editor, Molecular and Cellular Proteomics

2004 Member, Editorial Board, Molecular Cell

2005 Editor, Methods in Enzymology, Volumes 398 and 399, Ubiquitin and Protein Degradation (Parts A and B)

Advisory and Review Panels

2001 Evaluation of NIH-funded National Center for Research Resources

2002 Consultant, 'Proteomics Planning Meeting', NIH

2002-2007 Member, NIH Study Section CDF-3

2003-2005 Member, Defense Sciences Study Group of the Institute for Defense Analysis

2003 Visiting Review Committee, Institute of Molecular Biology, Academia Sinica, Taiwan

2006 Member, Selection Committee for ASCB Early Career Life Scientist Award

2006 Member, Presidential Search Committee, California Institute of Technology

2007 Chair, Selection Committee for ASCB Early Career Life Scientist Award

2009 Member, HHMI Policy Advisory Group

2010-2013 Member, ASCB Council

2010 Visiting Review Committee, King Abdul-Azziz University (Jeddah), King Abdullah University of Science and Technology (Thuwal), King Faisal University of Petroleum and Minerology (Dammam), King Saud University (Riyadh), Saudi Arabia

Teaching Activities

1985 Berkeley, Spring semester. Teaching Assistant, Biochemistry Lab

1986 Berkeley, Spring semester. Teaching Assistant, Biochemistry Lecture

1988 Berkeley, Spring semester. Instructor, Molecular Analysis of Mitosis

1995-2002 Caltech, Spring semester. Instructor, Bi10 Undergraduate Introductory Molecular Biology Lecture/Lab

1996-2002 Caltech, Fall semester. Co-instructor, Bi226 Genetics Graduate Seminar

1997 and 1999 Caltech, Winter semester. Instructor, Principles of Biological Analysis

1999-2010 Caltech, Fall semester. Instructor, Bi250 Adventures in Biology Graduate Course

2011-present Caltech, Spring semester. Co-instructor, Bi9 Cell Biology

Technology Transfer

2000 U.S. Patent 6,165,731: Assay for the ubiquitination-promoting activity of human proteins

2000 U.S. Patent 6,413,725: Biochemical assay to monitor the ubiquitin ligase activities of cullins

2004 U.S. Patent 6,713,267: Biochemical assay to monitor the ubiquitin ligase activities of cullins

2005 U.S. Patent 6,846,663: Regulation of target protein activity through modifier proteins

2006 U.S. Patent 7,041,298 B2: Proteolysis targeting chimeric pharmaceutical

2007 U.S. Patent 7,208,157: Proteolysis targeting chimeric pharmaceutical

2007 U.S. Patent 7,279,317: Modulation of COP9 signalsome isopeptidase activity

2007 U.S. Patent 7,291,494: Regulation of target protein activity through modifier proteins

2008 U.S. Patent 7,279,317: Modulation of COP9 signalsome isopeptidase activity

Bibliography

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2. Deshaies, R.J., Fish, L.E., and Jagendorf, A.T. (1984). Permeability of chloroplast envelopes to Mg2+. Effects on protein synthesis. Plant Physiol. 74, 956-961.

3. Deshaies, R.J., and Schekman, R. (1987). A yeast mutant defective at an early stage in import of secretory protein precursors into the endoplasmic reticulum. J. Cell Biol. 105, 633-645.

4. Deshaies, R.J., Koch, B.D., Werner-Washburne, M., Craig, E.A., and Schekman, R. (1988). 70 kD stress protein homologues facilitate translocation of secretory and mitochondrial precursor polypeptides. Nature 332, 800-805.

5. Bohni, P.C., Deshaies, R.J., and Schekman, R. (1988). SEC11 is required for signal peptide processing and yeast cell growth. J. Cell Biol. 106, 1035-1042.

6. Deshaies, R.J., Koch, B.D., and Schekman, R. (1988). The role of stress proteins in membrane biogenesis. Trends Biochem. Sci. 13, 384-388.

7. Deshaies, R.J., Kepes, F., and Bohni, P.C. (1989). Genetic dissection of the early stages of protein secretion in yeast. Trends Genet. 5, 87-93.

8. Deshaies, R.J., and Schekman, R. (1989). SEC62 encodes a putative membrane protein required for protein translocation into the yeast endoplasmic reticulum. J. Cell Biol. 109, 2653-2664.

9. Rothblatt, J.A., Deshaies, R.J., Sanders, S.L., Daum, G., and Schekman, R. (1989). Multiple genes are required for proper insertion of secretory proteins into the endoplasmic reticulum in yeast. J. Cell Biol. 109, 2641-2652.

10. Deshaies, R.J. and Schekman, R. (1990). Structural and functional dissection of Sec62p, a membrane-bound component of the yeast endoplasmic reticulum protein import machinery. Mol. Cell. Biol. 10, 6024-6035.

11. Deshaies, R.J., Feldheim, D., Sanders, S., and Schekman, R. (1990). Yeast Sec proteins involved in translocation into the endoplasmic reticulum are assembled into a membrane-bound multisubunit complex. Nature 349, 806-808.

12. Stirling, C.J., Rothblatt, J., Hosobuchi, M., Deshaies, R., and Schekman, R. (1992). Protein translocation mutants defective in the insertion of integral membrane proteins into the endoplasmic reticulum. Mol. Biol. Cell 3, 129-142.

13. Esnault, Y., Blondel, M.O., Deshaies, R.J., Schekman, R. and Kepes, F. (1993). The yeast SSS1 gene is essential for secretory protein translocation and encodes a conserved protein of the endoplasmic reticulum. EMBO J. 12, 4083-4093.

14. Booher, R.N., Deshaies, R.J. and Kirschner, M.W. (1993). Properties of Saccharomyces cerevisiae wee1 and its differential regulation of p34CDC28 in response to G1 and G2 cyclins. EMBO J. 12, 3417-3426.

15. Li, J.J. and Deshaies, R. J. (1993). Exercising self-restraint: discouraging illicit acts of S and M in eukaryotes. Cell 74, 223-226.

16. Deshaies, R.J. (1995). Make it or break it: the role of ubiquitin-dependent proteolysis in cellular regulation. Trends Cell Bio.5, 428-434.

17. Deshaies, R.J., Chau, V., and Kirschner, M.W. (1995). Ubiquitination of the G1 cyclin Cln2p by a Cdc34p-dependent pathway. EMBO J. 14, 303-312.

18. Deshaies, R.J. and Kirschner, M.W. (1995). G1 cyclin-dependent activation of p34CDC28 in vitro. Proc. Natl. Acad. Sci. USA 92, 1182-1186.

19. Gerber, M.R., Farrell, A., Deshaies, R.J., Herskowitz, I. and Morgan, D.O. (1995). CDC37 is required for association of the protein kinase CDC28 with G1 and mitotic cyclins. Proc. Natl. Acad. Sci. USA 92, 4651-4655.

20. Deshaies, R.J. (1995). The self-destructive personality of a cell cycle in transition. Curr. Opin. Cell Biol. 7, 781-789.

21. Banerjee, A., Deshaies, R.J., and Chau, V. (1995). Characterization of a dominant negative mutant of the cell cycle ubiquitin-conjugating enzyme Cdc34. J. Biol. Chem.270, 26209-26215.

22. King, R., Peters, J, Deshaies, R.J., and Kirschner, M. (1996). Role of ubiquitin-mediated proteolysis in cell cycle regulation. Science 274, 1652-1659.

23. Deshaies, R.J. (1997). Phosphorylation and proteolysis: partners in the regulation of cell division in budding yeast. Curr. Opin. Genet. Dev. Biol. 7, 7-16.

24. Verma, R., Chi, Y. and Deshaies, R.J. (1997). Cell-free ubiquitination in the regulation of cell division in budding yeast. Methods Enzymol. 283, 366-376.

25. Verma, R., Feldman, R.M.R., and Deshaies, R.J. (1997). SIC1 is ubiquitinated in vitro by a pathway that requires CDC4, CDC34, and cyclin/CDK activities. Mol. Biol.Cell 8, 1427-1437.

26. Verma, R., Annan, R., Huddleston, M., Carr, S., Reynard, G., and Deshaies, R.J. (1997). Phosphorylation of Sic1p by G1 cyclin/Cdk is required for its degradation and entry into S phase. Science 278, 455-460.

27. Feldman, R.M.R., Correll, C.C., Kaplan, K.B., and Deshaies, R.J. (1997). A Complex of Cdc4, Skp1, and Cdc53/Cullin Catalyzes Ubiquitination of the Phosphorylated CDK Inhibitor Sic1. Cell 91, 221-230.

28. Henchoz, S., Chi, Y., Catarin, B., Herskowitz, I., Deshaies, R.J., and Peter, M. (1997). Phosphorylation and ubiquitin-dependent degradation of the cyclin-dependent kinase inhibitor Far1p in budding yeast. Genes Dev. 11, 3046-3060.

29. Lyapina, S.L., Correll, C.C., Kipreos, E.T., and Deshaies, R.J. (1998). Human CUL1 forms an evolutionarily conserved ubiquitin ligase complex (SCF) with SKP1 and an F-box protein. Proc. Natl. Acad. Sci. USA 95, 7451-7456.

30. Peters, J.M., King, R.W., and Deshaies, R.J. (1998). Cell cycle control by ubiquitin-dependent proteolysis. In Ubiquitin and the Biology of the Cell. ed. J.M. Peters et al. Plenum Press, NY.

31. Shou, W., Seol, J.H., Shevchenko, A., Baskerville, C., Moazed, D., Chen, Z.W.S., Jang, J., Shevchenko, A., Charbonneau, H., and Deshaies, R.J. (1999). Exit from mitosis triggered by Tem1-dependent release of the protein phosphatase Cdc14 from nucleolar RENT complex. Cell 97, 233-244.

32. Deshaies R.J., and Jacks, T. (1999). Cell multiplication peering in and peering out: regulation of and by the cell cycle. Current Opin. in Cell Biol. 11, 705-707.

33. Straight, A.F., Shou, W., Dowd, G.J., Turck, C.W., Deshaies, R.J., Johnson, A.D., and Moazed, D. (1999). Net1, a Sir2-associated nucleolar protein required for rDNA silencing and nucleolar integrity. Cell, 97, 245-256.

34. Seol, J.H., Feldman, R.M.R., Zachariae, W., Shevchenko, A., Correll, C.C., Lyapina, S., Chi, Y., Galova, M., Claypool, J., Sandmeyer, S., Nasmyth, K., Shevchenko, A., and Deshaies, R.J. (1999). Cdc53/cullin and the essential Hrt1 RING-H2 subunit of SCF define a ubiquitin ligase module that activates the E2 enzyme Cdc34. Genes Dev. 13, 1614-1626.

35. Freed, E., Lacey, K.R., Huie, P., Lyapina, S.A., Deshaies, R.J., Stearns, T., and Jackson, P.K. (1999). Components of an SCF ubiquitin ligase localize to the centrosome and regulate the centrosome duplication cycle. Genes Dev. 17, 2242-57.

36. Deshaies, R.J. (1999). SCF and cullin/RING H2-based ubiquitin ligases. Annu. Rev. Cell Dev. Biol. 15, 435-467.

37. Verma, R. and Deshaies, R.J. (2000). A proteasome howdunit: the case of the missing signal. Cell, 101, 341-344.

38. Deshaies, R.J. and Meyerowitz, E.M. (2000). COP1 patrols the night beat. Nature Cell Biol. 2, E102-E104.

39. Reynard, G.J., Reynolds, W., Verma, R., and Deshaies, R.J. (2000). CKS1 is required for G1 cyclin/CDK activity in budding yeast. Mol. Cell Biol. 20, 5858-5864.

40. Verma, R., Chen, S., Feldman, R., Schieltz, D., Yates, J., and Deshaies, R.J. (2000). Proteasomal proteomics: identification of nucleotide-sensitive proteasome-interacting proteins by mass spectrometric analysis of affinity-purified proteasomes. Mol. Biol. Cell 11, 3425-3439.

41. Blondel, M., Galan, J.M., Chi, Y., Lafourcade, C., Longaretti, C., Deshaies, R.J., and Peter, M. (2000). Nuclear-specific degradation of Far1 is controlled by the localization of the F-box protein Cdc4. EMBO J. 19, 6085-6097.

42. Annan, R.S, Huddleston, M.J., Verma, R., Deshaies, R.J., and Carr, S.A. (2001). A multidimensional electrospray MS-based approach to phosphopeptide mapping. Anal. Chem. 73, 393-404.

43. Lippincott, J., Shannon, K.B., Shou, W., Deshaies, R.J., and Li, R. (2001). The Tem1 small GTPase controls actomyosin and septin dynamics during cytokinesis. Journal of Cell Science 7,1379-86.

44. Traverso, E.E., Baskerville, C., Liu, Y., Shou, W., James, P., Deshaies, R.J. and Charbonneau, H. (2001). Characterization of the net1 cell cycle-dependent regulator of the Cdc14 phosphatase from budding yeast. J Biol. Chem. 276, 21924-21931.

45. Seol, J.H., Shevchenko, A., Shevchenko, A., and Deshaies, R.J. (2001). Skp1 forms multiple protein complexes, including RAVE, a regulator of V-ATPase assembly. Nature Cell Biol. 4, 384-91.

46. Galan, J.M., Wiederkehr, A., Seol, J.H., Deshaies, R.J., Riezman, H., and Peter, M. (2001). Skp1p and the F-box protein Rcy1p form a non-SCF complex involved in recycling of the SNARE Snc1p in yeast. Mol. Cell Biol. 9, 3105-17.

47. Chi, Y., Huddleston, M.J., Zhang, X., Young, R.A., Annan, R.S., Carr, S.A., and Deshaies, R.J. (2001). Negative regulation of Gcn4 and Msn2 transcription factors by Srb10 cyclin-dependent kinase, Genes Dev. 15, 1078-1092.

48. Schwechheimer, C., Serino, G., Callis, J., Crosby, W.L., Lyapina, S., Deshaies, R.J., Gray, W.M., Estelle, M., and Deng, X.W. (2001). Interactions of COP9 Signalosome with the E3 ubiquitin ligase SCFTIR1 in mediating auxin response. Science 292, 1379-82.

49. Lyapina, S., Cope, G., Shevchenko, A., Serino, G., Tsuge, T., Zhou, C., Wolf, D.A., Wei, N., Shevchenko, A., and Deshaies, R.J. (2001). Promotion of NEDD8-CUL1 conjugate cleavage by COP9 Signalosome. Science 292, 1382-1385.

50. Mah, A.S., Jang, J., and Deshaies R.J. (2001). Protein kinase Cdc15 activates the Dbf2-Mob1 kinase complex. Proc. Natl. Acad. Sci. USA, 15, 7325-30.

51. Sakamoto, K.M., Kim, K.B., Kumagai, A., Mercurio, F., Crews, C.M., and Deshaies, R.J. (2001). Protacs: chimeric molecules that target proteins to the SCF complex for ubiquitination and degradation. Proc. Natl. Acad. Sci. USA 15, 8554-9.

52. Zhou, C., Seibert, V., Geyer, R., Rhee, E., Lyapina, S., Cope, G., Deshaies R.J., and Wolf, D.A. (2001). The fission yeast COP9/ signalosome is involved in cullin modification by ubiquitin-related Ned8p, BMC Biochemistry, 2, 7.

53. Shou, W., Sakamoto, K.M., Keener, J., Morimoto, K.W., Traverso, E.E,. Azzam, R., Hoppe, G.J., Feldman, R.M.R., DeModena, J., Moazed, D., Charbonneau, H., Nomura, M., and Deshaies. R.J. (2001). Net1 stimulates RNA polymerase I transcription and regulates nucleolar structure independently of controlling mitotic exit. Mol. Cell 8, 45-55.

54. Verma, R., McDonald, W.H., Yates, J.R. III, and Deshaies, R.J. (2001). Selective degradation of ubiquitinated Sic1 by purified 26S proteasome yields fully active S phase cyclin-Cdk. Mol. Cell 8, 439-48.

55. Wu, G., Lyapina, S., Das, I., Li, J., Guerney, M., Chui, I., Deshaies R.J., and Kitajewski, J. (2001). SEL-10, a negative regulator of notch signaling, targets notch for ubiquitin-mediated protein degradation, MCB 21, 7403-15.

56. Deshaies, R.J., and Eilers, M. (2001). Editorial Review: Cell Multiplication. Curr. Opin. Cell Biol. 13, 729-730.

57. Deshaies, R.J. and Ferrell, J.E. (2001). Multisite phosphorylation and the countdown to S phase. Cell 107, 819-822.

58. Deshaies, R.J., Seol, J.H., McDonald, W.H., Cope, G., Lyapina, S.,Shevchenko, A., Shevchenko A., Verma, R. and Yates, J.R. (2002). Charting the protein complexome in yeast by mass spectrometry. Mol. Cell. Prot. 1, 3-10.

59. Shou, W., and Deshaies, R.J. (2002). Multiple telophase arrest bypassed (tab) mutants alleviate the essential requirement for Cdc15 in exit from mitosis in S. cerevisiae. BMC Genet 3,4.

60. Shou, W., Azzam, R., Chen, S.L., Huddleston, M.J., Baskerville, C., Charbonneau, H., Annan, R.S., Carr, S.A., and Deshaies, R.J. (2002). Cdc5 influences phosphorylation of Net1 and disassembly of the RENT complex. BMC Mol Biol. 3, 3.

61. Shou, W., Verma, R., Annan, R.S., Huddleston, M.J., Chen, S.L., and Deshaies R.J. (2002). Mapping phosphorylation sites in proteins by mass spectrometry. Methods Enzymol. 351, 279-296.

62. Loughrey, C.S., Huddleston, M.J., Shou, W., Deshaies, R.J., Annan, R.S., and Carr, S.A. (2002). Mass spectrometry-based methods for phosphorylation site mapping of hyperphosphorylated proteins applied to Net1, a regulator of exit from mitosis in yeast. Mol. Cell Prot. 1, 186-96.

63. Verma, R., Aravind L., Oania, R., McDonald, W.H., Yates, J. R. III, Koonin, E.V. and Deshaies, R.J. (2002). Role of Rpn11 metalloprotease in deubiquitination and degradation by the 26S proteasome. Science 298, 611-615.

64. Cope, G.A., Suh, G.S., Aravind, L., Schwarz, S.E., Zipursky, S.L., Koonin, E.V. and Deshaies, R.J. (2002). Role of predicted metalloprotease motif of Jab1/Csn5 in cleavage of NEDD8 from CUL1. Science 298, 608-611.

65. Park C.J., Song S., Lee P.R., Shou W., Deshaies R.J. and Lee K.S. (2003). Loss of CDC5 function in saccharomyces cerevisiae leads to defects in Swe1p regulation and Bfa 1p/Bub2p-independent cytokinesis. Genetics 163, 21-33.

66. Petroski, M.D and Deshaies, R.J. (2003). Context of multiubiquitin chain attachment influences the rate of Sic1 degradation. Mol. Cell 11, 1435-44.

67. Petroski, M.D and Deshaies, R.J. (2003). Redundant degrons ensure the rapid destruction of sic1 at the g1 /s transition of the budding yeast cell cycle. Cell Cycle 2, 410-1.

68. Cope, G.A. and Deshaies, R.J. (2003). COP9 signalosome: a multifunctional regulator of SCF and other cullin-based ubiquitin ligases. Cell 114, 663-71.

69. Lipford, J.R. and Deshaies, R.J. (2003). Diverse roles for ubiquitin-dependent proteolysis in transcriptional activation. Nat. Cell Biol. 5, 845-50.

70. Sakamoto, K.M., Kim, K.B., Verma, R., Ransick, A., Stein, B., Crews, C.M., and Deshaies, R.J. (2003). Development of protacs to target cancer-promoting proteins for ubiquitination and degradation. Mol Cell Proteomics 2, 1350-1358.

71. Ambroggio, X.I., Rees, D.C., and Deshaies, R.J. (2004). JAMM: A metalloprotease-like zinc site in the proteasome and signalosome. PLOS Biol. 2, 0113-0119.

72. Graumann, J., Dunipace, L.A., Seol, J.H., McDonald, W.H., Yates, J.R. III, Wold, B.J., and Deshaies, R.J. (2003). Applicability of TAP-MudPIT to pathway proteomics in yeast. Mol. Cell. Proteomics 3, 266-237.

73. Schneekloth, J.S. Jr., Fonseca, F.N., Koldobskiy, M., Mandal, A., Deshaies, R., Sakamoto, K., and Crews, C.M. (2004). Chemical genetic control of protein levels: selective in vivo targeted degradation. J. Am. Chem. Soc. 126, 3748-3754.

74. Wertz, I.E., O'Rourke, K.M., Zhang, Z., Dornan, D., Arnott, D., Deshaies, R.J., and Dixit, V.M. (2004). Human De-etiolated-1 regulates cJun by assembling a CUL 4A ubiquitin ligase. Science 303, 1371-1374.

75. Verma, R., Oania, R., Graumann, J., and Deshaies, R.J. (2004). Multiubiquitin chain receptors define a layer of substrate selectivity in the ubiquitin-proteasome system. Cell 118, 99-110.

76. Azzam, R., Chen, S.L., Shou, W., Mah, A.S., Alexandru, G., Nasmyth, K., Annan, R.S., Carr, S.A., and Deshaies, R.J. (2004). Phosphorylation by cyclin B-Cdk underlies release of mitotic exit. Science 305, 516-519.

77. Verma, R., Peter, N.R., Tochtrop, G.P., Sakamoto, K.M., D'Onofrio, M., Varadan, R., Fushman, D., Deshaies, R.J., and King, R.W. (2004). Inhibition of proteasome-dependent degradation by a small molecule that binds the ubiquitin chain. Science 306, 117-120.

78. Petroski, M.D. and Deshaies, R. J. (2005). Function and regulation of cullin-RING ubiquitin ligases. Nat. Rev. Mol. Cell. Biol. 6, 9-20.

79. Mayor, T., Lipford, J.R., Graumann, J., Smith, G.T., and Deshaies, R.J. (2005). Analysis of poly-ubiquitin conjugates reveals that the Rpn10 substrate receptor contributes to the turnover of multiple proteasome targets. Mol. Cell Proteomics 4, 741-751.

80. Lipford, J.R., Smith, G.T., Chi, Y., and Deshaies, R.J. (2005). A putative stimulatory role for activator turnover in gene expression. Nature 438, 113-116.

81. Mah, A.S., Elia, A.E.H., Devgan, G, Ptacek, J., Schutkowski, M., Snyder, M., Yaffe, M.B., and Deshaies, R.J. (2005). Substrate specificity analysis of protein kinase complex Dbf20Mob1 by peptide library and proteome array screening. BMC Biochemistry 6, 22.

82. Mayor, T. and Deshaies, R.J. (2005). Two-step affinity purification of multiubiquitylated proteins from Saccharomyces cerevisiae. Methods Enzymol. 399, 385-392.

83. Verma, R. and Deshaies, R.J. (2005). Assaying degradation and deubiquitination of a ubiquitinated substrate by purified 26S proteasomes. Methods Enzymol. 398, 391-399.

84. Petroski, M.D. and Deshaies, R.J. (2005). In vitro reconstitution of SCF substrate ubiquitination with purified proteins. Methods Enzymol. 398, 143-158.

85. Petroski, M.D. and Deshaies, R.J. (2005). Mechanism of lysine 48-linked ubiquitin-chain synthesis by the cullin-RING ubiquitin-ligase complex SCF-Cdc34. Cell 123, 1107-1120.

86. Cope, G.A. and Deshaies, R.J. (2006). Targeted silencing of JabI /Csn5 in human cells downregulates SCF activity through reduction of F-box protein levels. BMC Biochemistry 7, 1.

87. Sharon, M., Taverner, T., Ambroggio, X.I., Deshaies, R.J., and Robinson, C.V. (2006). Structural organization of the 19% proteasome lid: Insights from MS of intact complexes. PloS Biol 4, 1314-1323 (e267).

88. Petroski, M.D., Kleiger, G., and Deshaies, R.J. (2006). Evaluation of a diffusion-driven mechanism for substrate ubiquitination by the SCF-Cdc34 ubiquitin ligase complex. Mol Cell 24, 523-534.

89. Ghaboosi, N. and Deshaies, R.J. (2006). A Conditional Yeast E1 Mutant Blocks the Ubiquitin­Proteasome Pathway and Reveals a Role for Ubiquitin Conjugates in Targeting Rad23 to the Proteasome. Mol. Bio. Cell 18, 1953-63.

90. Mayor, T., Graumann, J., Bryan, J., Macoss, M.J., and Deshaies, R.J. (2007). Quantitative profiling of ubiquitylated proteins releals protasome substrates and the substrate repertoire influenced by the Rpn10 receptor pathway. Mol. Cell. Proteomics, Mol. Cell. Proteomics 6, 1885-1895.

91. Haririnia, A., Verma, R., Purohit, N., Twarog, M.Z., Deshaies, R.J., Bolon, D., and Fushman, D. (2008). Mutations in the hydrophobic core of ubiquitin differentially affect its recognition by receptor proteins. J. Mol. Biol. 375, 979-996.

92. Goh, A.M., Walters, J.K., Elsasser, S., Verma, R., Deshaies, R.J., Finley, D., and Howley, P.M. (2008). Components of the ubiquitin-proteasome pathway compete for surfaces on Rad32 family proteins. BMC Biochem. 9, 4.

93. Alexandru, G., Graumann, J., Smith, G.T., Kolawa, N.J., Fang, R., and Deshaies, R.J. (2008). UBXD7 binds multiple ubiquitin ligases and implicates p97 in HIF1a turnover. Cell 134, 804-816.

94. Saha, A. and Deshaies, R. J. (2008). Multimodal activation of the ubiquitin ligase SCF by Nedd8 conjugation. Mol. Cell 32, 21-31.

95. Rodriguez-Gonzalez, A., Cyrus, K., Salcius, M., Kim, K., Crews, C.M., Deshaies, R.J., and Sakamoto, K.M. (2008). Targeting steroid hormone receptors for ubiquitination and degradation in breast and prostate cancer. Oncogene 27, 7201-7211.

96. Mohl, D.A., Huddleston, M.J., Collingwood, T.S., Annan, R.S., and Deshaies, R.J. (2009). Dbf2-Mob1 drives relocalization of protein phosphatase Cdc14 to the cytoplasm during exit from mitosis. J. Cell Biol. 184, 527-539.

97. Machida, K., Tsukamoto, H., Mkrtchyan, H., Duan, L., Dynnyk, A., Liu, H.M., Asahina, K., Govindarajan, S., Ray, R., Ou, J.H., Seki, E., Deshaies, R., Miyake, K., Lai, M.M. (2009). Toll-like receptor 4 mediates synergism between alcohol and HCV in hepatic oncogenesis involving stem cell marker Nanog. Proc. Nat. Acad. Sci. USA 106, 1548-1553.

98. Oh, Y.M., Kwon, Y.E., Kim, J.M., Bae, S.J., Lee, B.K., Yoo, S.J., Chung, C.H., Deshaies R.J., Seol, J.H. (2009) Chfr is linked to tumour metastasis through the downregulation of HDAC1. Nat. Cell Biol. 11, 295-302.

99. Deshaies, R.J. (2009). Drug discovery: Fresh target for cancer therapy (News & Views). Nature 458, 709-710.

100. Deshaies, R.J. and Joazeiro, C.A.P. (2009). RING domain E3 ubiquitin ligases. Annu. Rev. Biochem. 78, 399-434.

101. Kleiger G, Hao B, Mohl DA, Deshaies RJ. (2009). The acidic tail of the CDC34 ubiquitin-conjugating enzyme functions in both binding to and catalysis with ubiquitin ligase SCFCDC4. J. Biol. Chem. 284, 36012-36023.

102. Kleiger, G., Saha, A., Lewis, S., Kuhlman, B., and Deshaies, R.J. (2009). Rapid E2-E3 assembly and disassembly enable processive ubiquitylation of cullin-RING ubiquitin ligase substrates. Cell 139, 957-968.

103. Pierce, N., Kleiger, G., Shan, S., and Deshaies, R.J. (2009). Detection of sequential ubiquitination on a millisecond time-scale. Nature 462, 615-619.

104. Radhakrishnan, S.K., Lee, C.S., Young, P., Beskow, A., Chan, J.Y., and Deshaies, R.J. (2010). Transcription factor Nrf1 mediates the proteasome recovery pathway after proteasome inhibition in mammalian cells. Mol. Cell 38, 17-28.

105. Radhakrishnan, S.K., Lee, C.S., Young, P., Beskow, A., Chan, J.Y., and Deshaies, R.J. (2010). Transcription factor Nrf1 mediates the proteasome recovery pathway after proteasome inhibition in mammalian cells. Mol. Cell 38,17-28.

106. Aghajan, M., Jonai, N., Flick, K., Fu, F., Luo, M., Cai, X., Ouni, I., Pierce, N., Tang, X., Lomenick, B., Damoiseaux, R., Hao, R., Del Moral, P.M., Verma, R., Li, Y., Li, C., Houk, K.N., Jung, M.E., Zheng, N., Huang, L., Deshaies, R.J., Kaiser, P., and Huang, J. (2010). Chemical genetics screen for enhancers of rapamycin identifies a specific inhibitor of an SCF family E3 ubiquitin ligase. Nat. Biotechnol. 28, 738-742.

107. Collins, G.A., Gomez, T.A., Deshaies, R.J., and Tansey, W.P. (2010). Combined chemical and genetic approach to inhibit proteolysis by the proteasome. Yeast 27, 965-974.

108. Tyrell, A., Flick, K., Kleiger, G., Zhang, H., Deshaies, R.J., and Kaiser, P. (2010). Physiologically relevant and portable tandem ubiquitin-binding domain stabilizes polyubiquitylated proteins. Proc. Natl. Acad. Sci. USA 107, 19796-19801.

109. Deshaies, R.J., Emberley, E.D., and Saha, A. (2010). Control of cullin-ring ubiquitin ligase activity by Nedd8. Subcell. Biochem., 54, 41-56.

110. Verma, R., Oania, R., Fang, R., Smith, G.T., and Deshaies, R.J. (2011). Cdc48/p97 Mediates UV-Dependent Turnover of RNA Pol II. Mol Cell. 41, 82-92.

111. Chou, T.F., Brown, S.J., Minond, D., Nordin, B.E., Li, K., Jones, A.C., Chase, P., Porubsky, P.R., Stoltz, B.M., Schoenen, F.J., Patricelli, M.P., Hodder, P., Rosen, H., and Deshaies, R.J. (2011) Reversible inhibitor of p97, DBeQ, impairs both ubiquitin-dependent and autophagic protein clearance pathways. Proc. Natl. Acad. Sci. USA 108, 4834-4839.

112. Saha, A., Lewis, S., Kleiger, G., Kuhlman, B., and Deshaies, R.J. (2011). Essential role for ubiquitin-ubiquitin-conjugating enzyme interaction in ubiquitin discharge from Cdc34 to substrate. Mol. Cell 42, 75-83.

113. Lee, J.E., Sweredoski, M.J., Graham, R.L., Kolawa, N.J., Smith, G.T., Hess, S., and Deshaies, R.J. (2010). The steady-state repertoire of human SCF ubiquitin ligase complexes does not require ongoing Nedd8 conjugation. Mol. Cell. Proteomics [Epublished ahead of print December 17, 2010].

114. Chou, T.F. and Deshaies, R.J. (2011). Quantitative cell-based protein degradation assays to identify and classify drugs that target the ubiquitin-proteasome system. J. Biol. Chem. [E-published ahead of print February 22, 2011].

115. Gomez, T.A., Kolawa, N., Gee, M., Sweredoski, M.J., and Deshaies, R.J. (2011) Identification of a functional docking site in the Rpn1 LRR domain for the UBA-UBL domain protein Ddi1. BMC Biol. 9, 33.

116. Rabut, G., Le Dez, G., Verma, R., Makhnevych, T., Knebel, A., Kurz, T., Boone, C., Deshaies, R.J. and Peter, M. (2011). The TFIIH Subunit Tfb3 Regulates Cullin Neddylation. Mol Cell. 43, 488-495.