The Program in Molecular Medicine at the University of Massachusetts Medical School was established in a new research building in 1989. Faculty include both clinical investigators and basic scientists, many of whom focus their research on human disease processes. The laboratory groups and core facilities that compose Molecular Medicine represent many disciplines in the bio-medical sciences: biochemistry and molecular biology, cell biology, medicine, immunology, molecular genetics and microbiology, pediatrics, pharmacology, physiology, genomics, bioinformatics and proteomics. This diverse scientific environment makes the Program an exceptional training ground for graduate students and postdoctoral fellows, who in turn contribute much to its vitality and excitement. This collection showcases publications and presentations written by faculty and researchers of the Program in Molecular Medicine.

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Publications from 2001

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MKK7 is an essential component of the JNK signal transduction pathway activated by proinflammatory cytokines, Cathy Tournier, Chen Dong, Tod K. Turner, Stephen N. Jones, Richard A. Flavell, and Roger J. Davis

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HAT activity is essential for CBP-1-dependent transcription and differentiation in Caenorhabditis elegans, Martin Victor, Yanxia Bei, Frederique Gay, Dominica Calvo, Craig C. Mello, and Yang Shi

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Activation of the Akt-related cytokine-independent survival kinase requires interaction of its phox domain with endosomal phosphatidylinositol 3-phosphate, Joseph V. Virbasius, Xi Song, Darcy P. Pomerleau, Yong Zhan, G. Wayne Zhou, and Michael P. Czech

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High-throughput yeast two-hybrid assays for large-scale protein interaction mapping, Albertha J. M. Walhout and Marc Vidal

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Protein interaction maps for model organisms, Albertha J. M. Walhout and Marc Vidal

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Requirement of the JIP1 scaffold protein for stress-induced JNK activation, Alan J. Whitmarsh, Chia-Yi Kuan, Norman J. Kennedy, Nyaya Kelkar, Tarik F. Haydar, John P. Mordes, Michael C. Appel, Aldo A. Rossini, Stephen N. Jones, Richard A. Flavell, Pasko Rakic, and Roger J. Davis

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Identification and characterization of yUAP/Sub2p, a yeast homolog of the essential human pre-mRNA splicing factor hUAP56, Meng Zhang and Michael R. Green

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The p40phox and p47phox PX domains of NADPH oxidase target cell membranes via direct and indirect recruitment by phosphoinositides, Yong Zhan, Joseph V. Virbasius, Xi Song, Darcy P. Pomerleau, and G. Wayne Zhou

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Determinants of the broad recognition of exocytic Rab GTPases by Mss4, Zhongyuan Zhu, Anna M. Delprato, Eric Lee Merithew, and David G. Lambright

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A helical turn motif in Mss4 is a critical determinant of Rab binding and nucleotide release, Zhongyuan Zhu, John J. Dumas, Susan E. Lietzke, and David G. Lambright

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Construction of centrosomes and spindle poles by molecular motor-driven assembly of protein particles, Wendy Cherie Zimmerman and Stephen J. Doxsey

Publications from 2000

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Unusual polymorphisms in human immunodeficiency virus type 1 associated with nonprogressive infection, Louis Alexander, Emma Weiskopf, Thomas C. Greenough, Nathan C. Gaddis, Marcy R. Auerbach, Malcolm H. Malim, Stephen J. O'Brien, Bruce D. Walker, John L. Sullivan, and Ronald C. Desrosiers

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Conserved Features of Chromatin Remodeling Enzymes: A Dissertation, Laurie A. Boyer

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Functional delineation of three groups of the ATP-dependent family of chromatin remodeling enzymes, Laurie A. Boyer, Colin Logie, Edgar Bonte, Peter B. Becker, Paul A. Wade, Alan P. Wolffe, Carl Wu, Anthony N. Imbalzano, and Craig L. Peterson

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Actin-related proteins (Arps): conformational switches for chromatin-remodeling machines, Laurie A. Boyer and Craig L. Peterson

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Roles of the histone H2A-H2B dimers and the (H3-H4)(2) tetramer in nucleosome remodeling by the SWI-SNF complex, Laurie A. Boyer, Xiao Shao, Richard H. Ebright, and Craig L. Peterson

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c-Jun NH(2)-terminal kinase inhibits targeting of the protein phosphatase calcineurin to NFATc1, Chi-Wing Chow, C Dong, Richard A. Flavell, and Roger J. Davis

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JNK1 is required for T cell-mediated immunity against Leishmania major infection, Stephanie L. Constant, Chen Dong, Derek D. Yang, Mark Allen Wysk, Roger J. Davis, and Richard A. Flavell

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Cell confluence-dependent remodeling of endothelial membranes mediated by cholesterol, Silvia Corvera, Carlo DiBonaventura, and Howard S. Shpetner

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Effect of HIV on thymic function before and after antiretroviral therapy in children, Daniel C. Douek, Richard A. Koup, Richard D. McFarland, John L. Sullivan, and Katherine Luzuriaga

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A role for phospholipase D in GLUT4 glucose transporter translocation, Masahiro Emoto, Jes K. Klarlund, Steve B. Waters, Vivian Hu, Joanne M. Buxton, Anil Chawla, and Michael P. Czech

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A green fluorescent protein-based reverse two-hybrid system: application to the characterization of large numbers of potential protein-protein interactions, Hideki Endoh, Albertha J. M. Walhout, and Marc Vidal

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Molecular determinants that mediate selective activation of p38 MAP kinase isoforms, Herve Enslen, Deborah Marie Brancho, and Roger J. Davis

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Genetic requirements for inheritance of RNAi in C. elegans, Alla Grishok, Hiroaki Tabara, and Craig C. Mello

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Perinuclear localization and insulin responsiveness of GLUT4 requires cytoskeletal integrity in 3T3-L1 adipocytes, Adilson L. Guilherme, Masahiro Emoto, Joanne M. Buxton, Sahana Bose, Rosanna Sabini, William E. Theurkauf, John D. Leszyk, and Michael P. Czech

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c-Jun N-terminal kinase (JNK) repression during the inflammatory response? Just say NO, J. Perry Hall, Eric Lee Merithew, and Roger J. Davis

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Snail/slug family of repressors: slowly going into the fast lane of development and cancer, Kirugaval Hemavathy, Shovon Imtiaz Ashraf, and Y. Tony Ip

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Human Slug is a repressor that localizes to sites of active transcription, Kirugaval Hemavathy, S C Guru, John E. Harris, J. Don Chen, and Y. Tony Ip

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The protein-tyrosine kinase fer associates with signaling complexes containing insulin receptor substrate-1 and phosphatidylinositol 3-kinase, Masanori Iwanishi, Michael P. Czech, and Andrew D. Cherniack

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SWI-SNF-mediated nucleosome remodeling: role of histone octamer mobility in the persistence of the remodeled state, Mariela Jaskelioff, Igor M. Gavin, Craig L. Peterson, and Colin Logie

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Interaction of a mitogen-activated protein kinase signaling module with the neuronal protein JIP3, Nyaya Kelkar, Shashi Gupta, Martin Dickens, and Roger J. Davis

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Distinct polyphosphoinositide binding selectivities for pleckstrin homology domains of GRP1-like proteins based on diglycine versus triglycine motifs, Jes K. Klarlund, William Tsiaras, John Holik, Anil Chawla, and Michael P. Czech

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The FYVE domain of early endosome antigen 1 is required for both phosphatidylinositol 3-phosphate and Rab5 binding. Critical role of this dual interaction for endosomal localization, Deirdre C. Lawe, Varsha Patki, Robin A. Heller-Harrison, David G. Lambright, and Silvia Corvera

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Structural basis of 3-phosphoinositide recognition by pleckstrin homology domains, Susan E. Lietzke, Sahana Bose, Thomas Charles Cronin, Jes K. Klarlund, Anil Chawla, Michael P. Czech, and David G. Lambright

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Distinct classes of yeast promoters revealed by differential TAF recruitment, Xiao-Yong Li, Sukesh R. Bhaumik, and Michael R. Green

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Early therapy of vertical human immunodeficiency virus type 1 (HIV-1) infection: control of viral replication and absence of persistent HIV-1-specific immune responses, Katherine Luzuriaga, Margaret M. McManus, Michelle D. Catalina, Shane Renee Mayack, Mark E. Sharkey, Mario Stevenson, and John L. Sullivan

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Carbon monoxide has anti-inflammatory effects involving the mitogen-activated protein kinase pathway, Leo E. Otterbein, Fritz H. Bach, Jawed Alam, Miguel P. Soares, Hong-Tao Lu, Mark Allen Wysk, Roger J. Davis, Richard A. Flavell, and Augustine M. K. Choi

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Chlamydomonas IFT88 and its mouse homologue, polycystic kidney disease gene tg737, are required for assembly of cilia and flagella, Gregory J. Pazour, Bethany L. Dickert, Yvonne Vucica, E. Scott Seeley, Joel L. Rosenbaum, George B. Witman, and Douglas G. Cole

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The unique catalytic subunit of sperm cAMP-dependent protein kinase is the product of an alternative Calpha mRNA expressed specifically in spermatogenic cells, Jovenal T. San Agustin, Curtis G. Wilkerson, and George B. Witman

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Persistence of episomal HIV-1 infection intermediates in patients on highly active anti-retroviral therapy, Mark E. Sharkey, Ian Teo, Thomas Greenough, Natalia Sharova, Katherine Luzuriaga, John L. Sullivan, R. Pat Bucy, Leondios G. Kostrikis, Ashley Haase, Claire Veryard, Raul E. Davaro, Sarah H. Cheeseman, Jennifer S. Daly, Carol A. Bova, Richard T. Ellison III, Brian Mady, Kwan Kew Lai, Graeme Moyle, Mark Nelson, Brian Gazzard, Sunil Shaunak, and Mario Stevenson

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Actin cytoskeleton: putting a CAP on actin polymerization, Victoria A. Stevenson and William E. Theurkauf

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Requirement of JNK for stress-induced activation of the cytochrome c-mediated death pathway, Cathy Tournier, Patricia M. Hess, Derek D. Yang, Jie Xu, Tod K. Turner, Anjaruwee S. Nimnual, Dafna Bar-Sagi, Stephen N. Jones, Richard A. Flavell, and Roger J. Davis

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Light intermediate chain 1 defines a functional subfraction of cytoplasmic dynein which binds to pericentrin, Sharon H. Tynan, Aruna Purohit, Stephen J. Doxsey, and Richard B. Vallee

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Yeast two-hybrid systems and protein interaction mapping projects for yeast and worm, Albertha J. M. Walhout, Simon J. Boulton, and Marc Vidal

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GATEWAY recombinational cloning: application to the cloning of large numbers of open reading frames or ORFeomes, Albertha J. M. Walhout, Gary F. Temple, Michael A. Brasch, James L. Hartley, Monique A. Lorson, Sander van den Heuvel, and Marc Vidal

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The Role of MKK3 in Mediating Signals to the p38 MAP Kinase Pathway: A Dissertation, Mark Allen Wysk

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Structural basis for substrate specificity of protein-tyrosine phosphatase SHP-1, Jian Yang, Zhiliang Cheng, Tian-Qi Niu, Xiaoshan Liang, Zhizhuang Joe Zhao, and G. Wayne Zhou

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Cytoplasmic dynein-mediated assembly of pericentrin and gamma tubulin onto centrosomes, Aaron Isadore Young, Jason B. Dictenberg, Aruna Purohit, Richard A. Tuft, and Stephen J. Doxsey

Publications from 1999

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The mesoderm determinant snail collaborates with related zinc-finger proteins to control Drosophila neurogenesis, Shovon Imtiaz Ashraf, Xiaodi Hu, John Roote, and Y. Tony Ip

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Integration of calcium and cyclic AMP signaling pathways by 14-3-3, Chi-Wing Chow and Roger J. Davis

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Requirement for transcription factor NFAT in interleukin-2 expression, Chi-Wing Chow, Mercedes Rincon, and Roger J. Davis

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Signaling mechanisms that regulate glucose transport, Michael P. Czech and Silvia Corvera

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Structural basis of activation and GTP hydrolysis in Rab proteins, John J. Dumas, Zhongyuan Zhu, Joseph L. Connolly, and David G. Lambright

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A novel nuclear export activity in HIV-1 matrix protein required for viral replication, Stefan A. Dupont, Natalia Sharova, Caryn DeHoratius, Ching-man A. Virbasius, Xiaochun Zhu, Alissa G. Bukrinskaya, Mario Stevenson, and Michael R. Green

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Role of protein kinase C in signal attenuation following T cell receptor engagement, Belen Fernandez, Michael P. Czech, and Herman Meisner

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A role for the yeast SWI/SNF complex in DNA replication, Joan Frances Flanagan and Craig L. Peterson

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Centrosome proteins: a major class of autoantigens in scleroderma, Irina Catrinel Gavanescu, Dolores Vazquez-Abad, J. McCauley, Jean-Luc Senecal, and Stephen J. Doxsey

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Long-term nonprogressive infection with human immunodeficiency virus type 1 in a hemophilia cohort, Thomas C. Greenough, Doreen B. Brettler, Frank Kirchhoff, Louis Alexander, Ronald C. Desrosiers, Stephen J. O'Brien, Mohan Somasundaran, Katherine Luzuriaga, and John L. Sullivan

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Interaction and specificity of Rel-related proteins in regulating Drosophila immunity gene expression, Zhiqiang Han and Y. Tony Ip

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An insertional mutant of Chlamydomonas reinhardtii with defective microtubule positioning, Cynthia J. Horst, Douglas J. Fishkind, Gregory J. Pazour, and George B. Witman (Cell motility and the cytoskeleton)

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Pre-mRNA splicing of IgM exons M1 and M2 is directed by a juxtaposed splicing enhancer and inhibitor, Julie L. C. Kan and Michael R. Green

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Cell cycle-regulated histone acetylation required for expression of the yeast HO gene, Jocelyn E. Krebs, Min-Hao Kuo, C. David Allis, and Craig L. Peterson

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ADP-ribosylation factor 6 as a target of guanine nucleotide exchange factor GRP1, Stephen E. Langille, Varsha Patki, Jes K. Klarlund, Joanne M. Buxton, John Holik, Anil Chawla, Silvia Corvera, and Michael P. Czech

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The mammalian homolog of the frog type II selenodeiodinase does not encode a functional enzyme in the rat, Jack L. Leonard, Deborah M. Leonard, Marjorie Safran, Rui Wu, Maria L. Zapp, and Alan P. Farwell

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Defective IL-12 production in mitogen-activated protein (MAP) kinase kinase 3 (Mkk3)-deficient mice, Hong-Tao Lu, Derek D. Yang, Mark Allen Wysk, Evelina Gatti, Ira Mellman, Roger J. Davis, and Richard A. Flavell

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Toll receptor-mediated Drosophila immune response requires Dif, an NF-kappaB factor, Xiangjun Meng, Bhupinder S. Khanuja, and Y. Tony Ip

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LC2, the chlamydomonas homologue of the t complex-encoded protein Tctex2, is essential for outer dynein arm assembly, Gregory J. Pazour, Anthony Koutoulis, Sharon E. Benashski, Bethany L. Dickert, Hong Sheng, Ramila S. Patel-King, Stephen M. King, and George B. Witman

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The hepatitis B pX protein promotes dimerization and DNA binding of cellular basic region/leucine zipper proteins by targeting the conserved basic region, Giovanni Perini, Elke Oetjen, and Michael R. Green

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Functional interaction between GCN5 and polyamines: a new role for core histone acetylation, Kerri Jeanne Pollard, Michael L. Samuels, Kimberly A. Crowley, Jeffrey C. Hansen, and Craig L. Peterson

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Direct interaction of pericentrin with cytoplasmic dynein light intermediate chain contributes to mitotic spindle organization, Aruna Purohit, Sharon H. Tynan, Richard B. Vallee, and Stephen J. Doxsey

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WRM-1 activates the LIT-1 protein kinase to transduce anterior/posterior polarity signals in C. elegans, Christian Ernest Rocheleau, Jun Yasuda, Tae Ho Shin, Rueyling Lin, Hitoshi Sawa, Hideyuki Okano, James R. Priess, Roger J. Davis, and Craig C. Mello

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Functional analysis of TFIID components, Wu-Cheng Shen, Lynne Marie Apone, Ching-man A. Virbasius, Xiao-Yong Li, M. Monsalve, and Michael R. Green

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MOM-4, a MAP kinase kinase kinase-related protein, activates WRM-1/LIT-1 kinase to transduce anterior/posterior polarity signals in C. elegans, Tae Ho Shin, Jun Yasuda, Christian Ernest Rocheleau, Rueyling Lin, Martha C. Soto, Yanxia Bei, Roger J. Davis, and Craig C. Mello

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The abnormal gene in X-linked lymphoproliferative syndrome, John L. Sullivan

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The rde-1 gene, RNA interference, and transposon silencing in C. elegans, Hiroaki Tabara, Madathia Sarkissian, William G. Kelly, Jamie Fleenor, Alla Grishok, Lisa Timmons, Andrew Z. Fire, and Craig C. Mello

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Crystal structure of the nuclear matrix targeting signal of the transcription factor acute myelogenous leukemia-1/polyoma enhancer-binding protein 2alphaB/core binding factor alpha2, Lei Tang, Bo Guo, Amjad Javed, Je-Yong Choi, Scott W. Hiebert, Jane B. Lian, Andre J. Van Wijnen, Janet L. Stein, Gary S. Stein, and G. Wayne Zhou

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The MKK7 gene encodes a group of c-Jun NH2-terminal kinase kinases, Cathy Tournier, Alan J. Whitmarsh, Julie Cavanagh, Tamera Barrett, and Roger J. Davis

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Profound misregulation of muscle-specific gene expression in facioscapulohumeral muscular dystrophy, Rossella Tupler, Giovanni Perini, Maria Antonietta Pellegrino, and Michael R. Green

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Protein interaction mapping in C. elegans using proteins involved in vulval development, Albertha J. M. Walhout, Raffaella Sordella, Xiaowei Lu, James L. Hartley, Gary F. Temple, Michael A. Brasch, Nicolas Thierry-Mieg, and Marc Vidal

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A genetic strategy to eliminate self-activator baits prior to high-throughput yeast two-hybrid screens, Albertha J. M. Walhout and Marc Vidal

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Requirement of mitogen-activated protein kinase kinase 3 (MKK3) for tumor necrosis factor-induced cytokine expression, Mark Allen Wysk, Derek D. Yang, Hong-Tao Lu, Richard A. Flavell, and Roger J. Davis

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The JIP group of mitogen-activated protein kinase scaffold proteins, Jun Yasuda, Alan J. Whitmarsh, Julie Cavanagh, Manoj Sharma, and Roger J. Davis

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Centrosome dynamics in living cells, Aaron Isadore Young, Richard A. Tuft, Walter A. Carrington, and Stephen J. Doxsey

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Amorphous no longer: the centrosome comes into focus, Wendy Cherie Zimmerman, Cynthia A. Sparks, and Stephen J. Doxsey

Publications from 1998

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Transcription sans TBP, Lynne Marie Apone and Michael R. Green

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Broad, but not universal, transcriptional requirement for yTAFII17, a histone H3-like TAFII present in TFIID and SAGA, Lynne M. Apone, Ching-man A. Virbasius, Frank C. P. Holstege, Jing Wang, Richard A. Young, and Michael R. Green

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Transcriptional control: repression by local chromatin modification, Shovon Imtiaz Ashraf and Y. Tony Ip

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Functional analysis of Tpr: identification of nuclear pore complex association and nuclear localization domains and a role in mRNA export, Peter Lawrence Bangs, Brian Burke, Christine M. Powers, Roger W. Craig, Aruna Purohit, and Stephen J. Doxsey

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Establishment of a functional human immunodeficiency virus type 1 (HIV-1) reverse transcription complex involves the cytoskeleton, Alissa G. Bukrinskaya, Beda Brichacek, Angela Mann, and Mario Stevenson

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Pericentrin and gamma-tubulin form a protein complex and are organized into a novel lattice at the centrosome, Jason B. Dictenburg, Wendy Cherie Zimmerman, Cynthia A. Sparks, Aaron Isadore Young, Charles A. Vidair, Yixian Zheng, Walter A. Carrington, Fredric S. Fay, and Stephen J. Doxsey

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Defective T cell differentiation in the absence of Jnk1, Chen Dong, Derek D. Yang, Mark Allen Wysk, Alan J. Whitmarsh, Roger J. Davis, and Richard A. Flavell

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Changes in thymic function with age and during the treatment of HIV infection, Daniel C. Douek, Richard D. McFarland, Phillip H. Keiser, Earl A. Gage, Janice M. Massey, Barton F. Haynes, Michael A. Polis, Ashley T. Haase, Mark B. Feinberg, John L. Sullivan, Beth D. Jamieson, Jerome A. Zack, Louis J. Picker, and Richard A. Koup

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Mechanism of sodium arsenite-mediated induction of heme oxygenase-1 in hepatoma cells. Role of mitogen-activated protein kinases, Kimberly K. Elbirt, Alan J. Whitmarsh, Roger J. Davis, and Herbert L. Bonkovsky

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Selective activation of p38 mitogen-activated protein (MAP) kinase isoforms by the MAP kinase kinases MKK3 and MKK6, Herve Enslen, Joel Raingeaud, and Roger J. Davis

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The cytoplasmic zinc finger protein ZPR1 accumulates in the nucleolus of proliferating cells, Zoya Galcheva-Gargova, Laxman Gangwani, Konstantin N. Konstantinov, Monique Mikrut, Steven J. Theroux, Tamar Enoch, and Roger J. Davis

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Interaction of ZPR1 with translation elongation factor-1alpha in proliferating cells, Laxman Gangwani, Monique Mikrut, Zoya Galcheva-Gargova, and Roger J. Davis

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Wilson disease in 1998: genetic, diagnostic and therapeutic aspects, John L. Gollan and Timothy J. Gollan

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Stimulation of IRS-1-associated phosphatidylinositol 3-kinase and Akt/protein kinase B but not glucose transport by beta1-integrin signaling in rat adipocytes, Adilson L. Guilherme and Michael P. Czech

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Cross-talk between insulin receptor and integrin alpha5 beta1 signaling pathways, Adilson L. Guilherme, Kevin Torres, and Michael P. Czech

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A conserved p38 mitogen-activated protein kinase pathway regulates Drosophila immunity gene expression, Zhiqiang Han, Herve Enslen, Xiaodi Hu, Xiangjun Meng, I-Huan Wu, Tamera Barrett, Roger J. Davis, and Y. Tony Ip