James A. Wohlschlegel, Ph.D.

Mailing Address:
UCLA Biol Chem
Box 951737
Los Angeles, CA 90095

Office Address:
BSRB 377A
615 Charles E. Young Dr. South
Los Angeles, CA 90095

Affiliations
Affiliations
Assistant Professor, Biological Chemistry
Member, Biochemistry, Biophysics & Structural Biology GPB Home Area, Cell & Developmental Biology GPB Home Area, Gene Regulation GPB Home Area, JCCC Gene Regulation Program Area, UCLA-DOE Institute for Genomics & Proteomics, themes
Research Interests
Signaling networks have emerged as the underlying regulatory system by which the many biological pathways required for sustaining life are coordinated. My laboratory uses a combination of biochemistry and proteomic mass spectrometry to understand the signaling networks mediated by the ubiquitin family of small protein modifications. Specifically, we are examining the role of two members of this family, ubiquitin and SUMO, in regulating key nuclear processes. Importantly, the deregulation of these two modification systems has been linked to the pathogenesis of many diseases including cancer, neurodegenerative diseases, and immune system disorders. Ubiquitin is a 76 amino acid protein that regulates the abundance and activity of a large number of cellular factors through its covalent attachment to lysines in target proteins. The specificity of this modification system is generated by a large family of ubiquitin ligases, each of which target a specific set of substrates for modification. We are currently characterizing a subset of these ubiquitin ligases that have been implicated in tumorigenesis. Using a combination of proteomic and biochemical tools, we are identifying the substrates of these ligases and working to understand how altering the modification state of these substrates can influence tumor progression. SUMO is another member of the ubiquitin family of small protein modifiers that plays a critical regulatory role in a number of different biological processes. We previously developed a series of proteomic tools that enabled us to characterize different aspects of this signaling pathway. These findings form the basis for ongoing work in my laboratory aimed at understanding how SUMO-regulated protein networks influence chromatin structure, cell cycle progression and genome stability and how misregulation of this pathway can play a critical role in tumorigenesis.
Biography

James Wohlschlegel received his B.S. in Biochemistry from Texas A&M University (College Station, TX) in 1997. He then went to graduate school at Harvard Medical School (Boston, MA) where he studied protein complexes regulating the initiation of DNA replication in the laboratory of Anindya Dutta. After completing his Ph.D. in 2002, James went to the Scripps Research Institute (La Jolla, CA) for postdoctoral training under the co-mentorship of John Yates (proteomic mass spectrometry) and Steven Reed (cell cycle regulation). James joined the Department of Biological Chemistry as an assistant professor in 2006.

Publications
Beck Josh R, Fung Connie, Straub Kurtis W, Coppens Isabelle, Vashisht Ajay A, Wohlschlegel James A, Bradley Peter J A Toxoplasma Palmitoyl Acyl Transferase and the Palmitoylated Armadillo Repeat Protein TgARO Govern Apical Rhoptry Tethering and Reveal a Critical Role for the Rhoptries in Host Cell Invasion but Not Egress. PLoS pathogens. 2013; 9(2): e1003162.
Kim Myoung Shin, Machida Yuka, Vashisht Ajay A, Wohlschlegel James A, Pang Yuan-Ping, Machida Yuichi J Regulation of error-prone translesion synthesis by Spartan/C1orf124. Nucleic acids research. 2013; 41(3): 1661-8.
Thivierge Caroline, Makil Neetha, Flamand Mathieu, Vasale Jessica J, Mello Craig C, Wohlschlegel James, Conte Darryl, Duchaine Thomas F Tudor domain ERI-5 tethers an RNA-dependent RNA polymerase to DCR-1 to potentiate endo-RNAi. Nature structural & molecular biology. 2013; 20(2): 244.
Du Jiamu, Zhong Xuehua, Bernatavichute Yana V, Stroud Hume, Feng Suhua, Caro Elena, Vashisht Ajay A, Terragni Jolyon, Chin Hang Gyeong, Tu Andy, Hetzel Jonathan, Wohlschlegel James A, Pradhan Sriharsa, Patel Dinshaw J, Jacobsen Steven E Dual binding of chromomethylase domains to H3K9me2-containing nucleosomes directs DNA methylation in plants. Cell. 2012; 151(1): 167-80.
Nie Minghua, Aslanian Aaron, Prudden John, Heideker Johanna, Vashisht Ajay A, Wohlschlegel James A, Yates John R, Boddy Michael N Dual recruitment of Cdc48 (p97)-Ufd1-Npl4 ubiquitin-selective segregase by small ubiquitin-like modifier protein (SUMO) and ubiquitin in SUMO-targeted ubiquitin ligase-mediated genome stability functions. The Journal of biological chemistry. 2012; 287(35): 29610-9.
Ausin Israel, Greenberg Maxim V C, Simanshu Dhirendra K, Hale Christopher J, Vashisht Ajay A, Simon Stacey A, Lee Tzuu-fen, Feng Suhua, Española Sophia D, Meyers Blake C, Wohlschlegel James A, Patel Dinshaw J, Jacobsen Steven E INVOLVED IN DE NOVO 2-containing complex involved in RNA-directed DNA methylation in Arabidopsis. Proceedings of the National Academy of Sciences of the United States of America. 2012; 109(22): 8374-81.
Stehling Oliver, Vashisht Ajay A, Mascarenhas Judita, Jonsson Zophonias O, Sharma Tanu, Netz Daili J A, Pierik Antonio J, Wohlschlegel James A, Lill Roland MMS19 assembles iron-sulfur proteins required for DNA metabolism and genomic integrity. Science (New York, N.Y.). 2012; 337(6091): 195-9.
Chen Xiao-Fen, Lehmann Lynn, Lin Justin J, Vashisht Ajay, Schmidt Ryan, Ferrari Roberto, Huang Chengyang, McKee Robin, Mosley Amber, Plath Kathrin, Kurdistani Siavash K, Wohlschlegel James, Carey Michael Mediator and SAGA have distinct roles in Pol II preinitiation complex assembly and function. Cell reports. 2012; 2(5): 1061-7.
Lehmann Lynn, Ferrari Roberto, Vashisht Ajay A, Wohlschlegel James A, Kurdistani Siavash K, Carey Michael Polycomb repressive complex 1 (PRC1) disassembles RNA polymerase II preinitiation complexes. The Journal of biological chemistry. 2012; 287(43): 35784-94.
Caro Elena, Stroud Hume, Greenberg Maxim V C, Bernatavichute Yana V, Feng Suhua, Groth Martin, Vashisht Ajay A, Wohlschlegel James, Jacobsen Steve E The SET-domain protein SUVR5 mediates H3K9me2 deposition and silencing at stimulus response genes in a DNA methylation-independent manner. PLoS genetics. 2012; 8(10): e1002995.
Thivierge Caroline, Makil Neetha, Flamand Mathieu, Vasale Jessica J, Mello Craig C, Wohlschlegel James, Conte Darryl, Duchaine Thomas F Tudor domain ERI-5 tethers an RNA-dependent RNA polymerase to DCR-1 to potentiate endo-RNAi. Nature structural & molecular biology. 2012; 19(1): 90-7.
Sun Yu, Vashisht Ajay A, Tchieu Jason, Wohlschlegel James A, Dreier Lars Voltage-dependent anion channels (VDACs) recruit Parkin to defective mitochondria to promote mitochondrial autophagy. The Journal of biological chemistry. 2012; 287(48): 40652-60.
Oberholzer Michael, Langousis Gerasimos, Nguyen HoangKim T, Saada Edwin A, Shimogawa Michelle M, Jonsson Zophonias O, Nguyen Steven M, Wohlschlegel James A, Hill Kent L Independent analysis of the flagellum surface and matrix proteomes provides insight into flagellum signaling in mammalian-infectious Trypanosoma brucei. Molecular & cellular proteomics : MCP. 2011; 10(10): M111.010538.
Lin Justin J, Lehmann Lynn W, Bonora Giancarlo, Sridharan Rupa, Vashisht Ajay A, Tran Nancy, Plath Kathrin, Wohlschlegel James A, Carey Michael Mediator coordinates PIC assembly with recruitment of CHD1. Genes & development. 2011; 25(20): 2198-209.
Smith Alias J, Chudnovsky Lorissa, Simoes-Barbosa Augusto, Delgadillo-Correa Maria G, Jonsson Zophonias O, Wohlschlegel James A, Johnson Patricia J Novel core promoter elements and a cognate transcription factor in the divergent unicellular eukaryote Trichomonas vaginalis. Molecular and cellular biology. 2011; 286(4): .
Lomenick Brett, Jung Gwanghyun, Wohlschlegel James A, Huang Jing Target identification using drug affinity responsive target stability (DARTS). Current protocols in chemical biology. 2011; 3(4): 163-180.
Law Julie A, Ausin Israel, Johnson Lianna M, Vashisht Ajay A, Zhu Jian-Kang, Wohlschlegel James A, Jacobsen Steven E A protein complex required for polymerase V transcripts and RNA- directed DNA methylation in Arabidopsis. Current biology : CB. 2010; 20(10): 951-6.
Spielewoy Nathalie, Guaderrama Marisela, Wohlschlegel James A, Ashe Mabelle, Yates John R, Wittenberg Curt Npr2, yeast homolog of the human tumor suppressor NPRL2, is a target of Grr1 required for adaptation to growth on diverse nitrogen sources. Eukaryotic cell. 2010; 9(4): 592-601.
de Miguel Natalia, Lustig Gil, Twu Olivia, Chattopadhyay Arnab, Wohlschlegel James A, Johnson Patricia J Proteome analysis of the surface of Trichomonas vaginalis reveals novel proteins and strain-dependent differential expression. Molecular & cellular proteomics : MCP. 2010; 9(7): 1554-66.
Hernandez Alfredo, Madina Bhaskara Reddy, Ro Kevin, Wohlschlegel James A, Willard Belinda, Kinter Mike T, Cruz-Reyes Jorge REH2 RNA helicase in kinetoplastid mitochondria: ribonucleoprotein complexes and essential motifs for unwinding and guide RNA (gRNA) binding. The Journal of biological chemistry. 2010; 285(2): 1220-8.
Vashisht Ajay A, Zumbrennen Kimberly B, Huang Xinhua, Powers David N, Durazo Armando, Sun Dahui, Bhaskaran Nimesh, Persson Anja, Uhlen Mathias, Sangfelt Olle, Spruck Charles, Leibold Elizabeth A, Wohlschlegel James A Control of iron homeostasis by an iron-regulated ubiquitin ligase. Science (New York, N.Y.). 2009; 326(5953): 718-21.
Konopka Genevieve, Bomar Jamee M, Winden Kellen, Coppola Giovanni, Jonsson Zophonias O, Gao Fuying, Peng Sophia, Preuss Todd M, Wohlschlegel James A, Geschwind Daniel H Human-specific transcriptional regulation of CNS development genes by FOXP2. Nature. 2009; 462(7270): 213-7.
Wohlschlegel James A Identification of SUMO-conjugated proteins and their SUMO attachment sites using proteomic mass spectrometry. Methods in molecular biology (Clifton, N.J.). 2009; 497(5): 33-49.
Chuang Li-Chiou, Teixeira Leonardo K, Wohlschlegel James A, Henze Martha, Yates John R, Méndez Juan, Reed Steven I Phosphorylation of Mcm2 by Cdc7 promotes pre-replication complex assembly during cell-cycle re-entry. Molecular cell. 2009; 35(2): 206-16.
Zhou Rui, Czech Benjamin, Brennecke Julius, Sachidanandam Ravi, Wohlschlegel James A, Perrimon Norbert, Hannon Gregory J Processing of Drosophila endo-siRNAs depends on a specific Loquacious isoform. RNA (New York, N.Y.). 2009; 15(10): 1886-95.
Lomenick Brett, Hao Rui, Jonai Nao, Chin Randall M, Aghajan Mariam, Warburton Sarah, Wang Jianing, Wu Raymond P, Gomez Fernando, Loo Joseph A, Wohlschlegel James A, Vondriska Thomas M, Pelletier Jerry, Herschman Harvey R, Clardy Jon, Clarke Catherine F, Huang Jing Target identification using drug affinity responsive target stability (DARTS). Proceedings of the National Academy of Sciences of the United States of America. 2009; 106(51): 21984-9.
Machida Yuichi J, Machida Yuka, Vashisht Ajay A, Wohlschlegel James A, Dutta Anindya The deubiquitinating enzyme BAP1 regulates cell growth via interaction with HCF-1. The Journal of biological chemistry. 2009; 284(49): 34179-88.
Zamudio Jesse R, Mittra Bidyottam, Chattopadhyay Arnab, Wohlschlegel James A, Sturm Nancy R, Campbell David A Trypanosoma brucei spliced leader RNA maturation by the cap 1 2'-O-ribose methyltransferase and SLA1 H/ACA snoRNA pseudouridine synthase complex. Molecular and cellular biology. 2009; 29(5): 1202-11.
Bellare Priya, Small Eliza C, Huang Xinhua, Wohlschlegel James A, Staley Jonathan P, Sontheimer Erik J A role for ubiquitin in the spliceosome assembly pathway. Nature structural & molecular biology. 2008; 15(5): 444-51.
Czech Benjamin, Malone Colin D, Zhou Rui, Stark Alexander, Schlingeheyde Catherine, Dus Monica, Perrimon Norbert, Kellis Manolis, Wohlschlegel James A, Sachidanandam Ravi, Hannon Gregory J, Brennecke Julius An endogenous small interfering RNA pathway in Drosophila. Nature. 2008; 453(7196): 798-802.
Usaite Renata, Wohlschlegel James, Venable John D, Park Sung K, Nielsen Jens, Olsson Lisbeth, Yates Iii John R Characterization of global yeast quantitative proteome data generated from the wild-type and glucose repression saccharomyces cerevisiae strains: the comparison of two quantitative methods. Journal of proteome research. 2008; 7(1): 266-75.
Reed Darien E, Huang Xinhua M, Wohlschlegel James A, Levine Michael S, Senger Kate DEAF-1 regulates immunity gene expression in Drosophila. Proceedings of the National Academy of Sciences of the United States of America. 2008; 105(24): 8351-6.
Olson Brian L, Hock M Benjamin, Ekholm-Reed Susanna, Wohlschlegel James A, Dev Kumlesh K, Kralli Anastasia, Reed Steven I SCFCdc4 acts antagonistically to the PGC-1alpha transcriptional coactivator by targeting it for ubiquitin-mediated proteolysis. Genes & development. 2008; 22(2): 252-64.
Simoes-Barbosa Augusto, Meloni Dionigia, Wohlschlegel James A, Konarska Maria M, Johnson Patricia J Spliceosomal snRNAs in the unicellular eukaryote Trichomonas vaginalis are structurally conserved but lack a 5'-cap structure. RNA (New York, N.Y.). 2008; 14(8): 1617-31.
Motoyama Akira, Xu Tao, Ruse Cristian I, Wohlschlegel James A, Yates John R Anion and cation mixed-bed ion exchange for enhanced multidimensional separations of peptides and phosphopeptides. Analytical chemistry. 2007; 79(10): 3623-34.
Zhu Wenge, Ukomadu Chinweike, Jha Sudhakar, Senga Takeshi, Dhar Suman K, Wohlschlegel James A, Nutt Leta K, Kornbluth Sally, Dutta Anindya Mcm10 and And-1/CTF4 recruit DNA polymerase alpha to chromatin for initiation of DNA replication. Genes & development. 2007; 21(18): 2288-99.
Venable John D, Wohlschlegel James, McClatchy Daniel B, Park Sung Kyu, Yates John R Relative quantification of stable isotope labeled peptides using a linear ion trap-Orbitrap hybrid mass spectrometer. Analytical chemistry. 2007; 79(8): 3056-64.
Sadygov, R. Wohlschlegel, J. Park, S. K. Xu, T. Yates, J. R., 3rd Central limit theorem as an approximation for intensity-based scoring function. Anal Chem. 2006; 78(1): 89-95.
de Bruin, R. A. Kalashnikova, T. I. Chahwan, C. McDonald, W. H. Wohlschlegel, J. Yates, J., 3rd Russell, P. Wittenberg, C. Constraining G1-specific transcription to late G1 phase: the MBF-associated corepressor Nrm1 acts via negative feedback. Mol Cell. 2006; 23(4): 483-96.
Duchaine, T. F. Wohlschlegel, J. A. Kennedy, S. Bei, Y. Conte, D., Jr. Pang, K. Brownell, D. R. Harding, S. Mitani, S. Ruvkun, G. Yates, J. R., 3rd Mello, C. C. Functional proteomics reveals the biochemical niche of C. elegans DCR-1 in multiple small-RNA-mediated pathways. Cell. 2006; 124(2): 343-54.
Wohlschlegel, J. A. Johnson, E. S. Reed, S. I. Yates, J. R., 3rd Improved identification of SUMO attachment sites using C-terminal SUMO mutants and tailored protease digestion strategies. J Proteome Res. 2006; 5(4): 761-70.
Raffa Grazia D, Wohlschlegel James, Yates John R, Boddy Michael N SUMO-binding motifs mediate the Rad60-dependent response to replicative stress and self-association. The Journal of biological chemistry. 2006; 281(38): 27973-81.
Sedgwick, C. Rawluk, M. Decesare, J. Raithatha, S. Wohlschlegel, J. Semchuk, P. Ellison, M. Yates, J. Stuart, D. Saccharomyces cerevisiae Ime2 phosphorylates Sic1 at multiple PXS/T sites but is insufficient to trigger Sic1 degradation. Biochem J. 2006; 399(1): 151-60.
Sedgwick Chantelle, Rawluk Matthew, Decesare James, Raithatha Sheetal, Wohlschlegel James, Semchuk Paul, Ellison Michael, Yates John, Stuart David Saccharomyces cerevisiae Ime2 phosphorylates Sic1 at multiple PXS/T sites but is insufficient to trigger Sic1 degradation. The Biochemical journal. 2006; 399(1): 151-60.
Raffa, G. D. Wohlschlegel, J. Yates, J. R., 3rd Boddy, M. N. Sumo-binding motifs mediate the RAD60-dependent response to replicative stress and self association. J Biol Chem. 2006; .
Martin, V. Chahwan, C. Gao, H. Blais, V. Wohlschlegel, J. Yates, J. R., 3rd McGowan, C. H. Russell, P. Sws1 is a conserved regulator of homologous recombination in eukaryotic cells. Embo J. 2006; 25(11): 2564-74.
Pebernard, S. Wohlschlegel, J. McDonald, W. H. Yates, J. R., 3rd Boddy, M. N. The Nse5-Nse6 dimer mediates DNA repair roles of the Smc5-Smc6 complex. Mol Cell Biol. 2006; 26(5): 1617-30.
Ernkvist, M. Aase, K. Ukomadu, C. Wohlschlegel, J. Blackman, R. Veitonmaki, N. Bratt, A. Dutta, A. Holmgren, L. p130-angiomotin associates to actin and controls endothelial cell shape. Febs J. 2006; 273(9): 2000-11.
Liu, J. Rivas, F. V. Wohlschlegel, J. Yates, J. R., 3rd Parker, R. Hannon, G. J. A role for the P-body component GW182 in microRNA function. Nat Cell Biol. 2005; 7(12): 1261-6.
Kaiser, P. Wohlschlegel, J. Identification of ubiquitination sites and determination of ubiquitin-chain architectures by mass spectrometry. Methods Enzymol. 2005; 399: 266-77.
Venable, J. D. Dong, M. Q. Wohlschlegel, J. Dillin, A. Yates, J. R. Automated approach for quantitative analysis of complex peptide mixtures from tandem mass spectra. Nat Methods. 2004; 1(1): 39-45.
Wohlschlegel, J. A. Johnson, E. S. Reed, S. I. Yates, J. R., 3rd Global analysis of protein sumoylation in Saccharomyces cerevisiae. J Biol Chem. 2004; 279(44): 45662-8.
Flick, K. Ouni, I. Wohlschlegel, J. A. Capati, C. McDonald, W. H. Yates, J. R. Kaiser, P. Proteolysis-independent regulation of the transcription factor Met4 by a single Lys 48-linked ubiquitin chain. Nat Cell Biol. 2004; 6(7): 634-41.
Jonsson, Z. O. Jha, S. Wohlschlegel, J. A. Dutta, A. Rvb1p/Rvb2p recruit Arp5p and assemble a functional Ino80 chromatin remodeling complex. Mol Cell. 2004; 16(3): 465-77.
Wohlschlegel, J. A. Yates, J. R. Proteomics: where's Waldo in yeast?. Nature. 2003; 425(6959): 671-2.
Wohlschlegel, J. A. Kutok, J. L. Weng, A. P. Dutta, A. Expression of geminin as a marker of cell proliferation in normal tissues and malignancies. Am J Pathol. 2002; 161(1): 267-73.
Wohlschlegel, J. A. Dhar, S. K. Prokhorova, T. A. Dutta, A. Walter, J. C. Xenopus Mcm10 binds to origins of DNA replication after Mcm2-7 and stimulates origin binding of Cdc45. Mol Cell. 2002; 9(2): 233-40.
Takeda, D. Y. Wohlschlegel, J. A. Dutta, A. A bipartite substrate recognition motif for cyclin-dependent kinases. J Biol Chem. 2001; 276(3): 1993-7.
Wohlschlegel, J. A. Dwyer, B. T. Takeda, D. Y. Dutta, A. Mutational analysis of the Cy motif from p21 reveals sequence degeneracy and specificity for different cyclin-dependent kinases. Mol Cell Biol. 2001; 21(15): 4868-74.
Dhar, S. K. Yoshida, K. Machida, Y. Khaira, P. Chaudhuri, B. Wohlschlegel, J. A. Leffak, M. Yates, J. Dutta, A. Replication from oriP of Epstein-Barr virus requires human ORC and is inhibited by geminin. Cell. 2001; 106(3): 287-96.
Wohlschlegel, J. A. Dwyer, B. T. Dhar, S. K. Cvetic, C. Walter, J. C. Dutta, A. Inhibition of eukaryotic DNA replication by geminin binding to Cdt1. Science. 2000; 290(5500): 2309-12.
Pinto, S. Quintana, D. G. Smith, P. Mihalek, R. M. Hou, Z. H. Boynton, S. Jones, C. J. Hendricks, M. Velinzon, K. Wohlschlegel, J. A. Austin, R. J. Lane, W. S. Tully, T. Dutta, A. latheo encodes a subunit of the origin recognition complex and disrupts neuronal proliferation and adult olfactory memory when mutant. Neuron. 1999; 23(1): 45-54.
Garza, A. G. Biran, R. Wohlschlegel, J. A. Manson, M. D. Mutations in motB suppressible by changes in stator or rotor components of the bacterial flagellar motor. J Mol Biol. 1996; 258(2): 270-85.