multiprotein complexes

Summary

Summary: Macromolecular complexes formed from the association of defined protein subunits.

Top Publications

  1. pmc AMPK phosphorylation of raptor mediates a metabolic checkpoint
    Dana M Gwinn
    Molecular and Cell Biology Laboratory, Dulbecco Center for Cancer Research, Salk Institute for Biological Studies, La Jolla, CA 92037, USA
    Mol Cell 30:214-26. 2008
  2. pmc Ragulator-Rag complex targets mTORC1 to the lysosomal surface and is necessary for its activation by amino acids
    Yasemin Sancak
    Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA
    Cell 141:290-303. 2010
  3. pmc Regulation of the mTOR complex 1 pathway by nutrients, growth factors, and stress
    Shomit Sengupta
    Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, MA 02142, USA
    Mol Cell 40:310-22. 2010
  4. pmc mTORC1 senses lysosomal amino acids through an inside-out mechanism that requires the vacuolar H(+)-ATPase
    Roberto Zoncu
    Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, MA 02142, USA
    Science 334:678-83. 2011
  5. pmc An ATP-competitive mammalian target of rapamycin inhibitor reveals rapamycin-resistant functions of mTORC1
    Carson C Thoreen
    Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA
    J Biol Chem 284:8023-32. 2009
  6. pmc The Rag GTPases bind raptor and mediate amino acid signaling to mTORC1
    Yasemin Sancak
    Whitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology MIT, Nine Cambridge Center, Cambridge, MA 02142, USA
    Science 320:1496-501. 2008
  7. ncbi SIN1/MIP1 maintains rictor-mTOR complex integrity and regulates Akt phosphorylation and substrate specificity
    Estela Jacinto
    Department of Physiology and Biophysics, UMDNJ Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA
    Cell 127:125-37. 2006
  8. ncbi Ablation in mice of the mTORC components raptor, rictor, or mLST8 reveals that mTORC2 is required for signaling to Akt-FOXO and PKCalpha, but not S6K1
    David A Guertin
    Whitehead Institute for Biomedical Research and Massachusetts Institute of Technology, Department of Biology, Cambridge, Massachusetts 02141, USA
    Dev Cell 11:859-71. 2006
  9. pmc Inhibition of mTORC1 leads to MAPK pathway activation through a PI3K-dependent feedback loop in human cancer
    Arkaitz Carracedo
    Cancer Genetics Program, Beth Israel Deaconess Cancer Center, Harvard Medical School, Boston, Massachusetts, USA
    J Clin Invest 118:3065-74. 2008
  10. pmc Ragulator is a GEF for the rag GTPases that signal amino acid levels to mTORC1
    Liron Bar-Peled
    Whitehead Institute for Biomedical Research and Massachusetts Institute of Technology, Department of Biology, Nine Cambridge Center, Cambridge, MA 02142, USA
    Cell 150:1196-208. 2012

Research Grants

Detail Information

Publications296 found, 100 shown here

  1. pmc AMPK phosphorylation of raptor mediates a metabolic checkpoint
    Dana M Gwinn
    Molecular and Cell Biology Laboratory, Dulbecco Center for Cancer Research, Salk Institute for Biological Studies, La Jolla, CA 92037, USA
    Mol Cell 30:214-26. 2008
    ..These findings uncover a conserved effector of AMPK that mediates its role as a metabolic checkpoint coordinating cell growth with energy status...
  2. pmc Ragulator-Rag complex targets mTORC1 to the lysosomal surface and is necessary for its activation by amino acids
    Yasemin Sancak
    Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA
    Cell 141:290-303. 2010
    ..Thus, Rag-Ragulator-mediated translocation of mTORC1 to lysosomal membranes is the key event in amino acid signaling to mTORC1...
  3. pmc Regulation of the mTOR complex 1 pathway by nutrients, growth factors, and stress
    Shomit Sengupta
    Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, MA 02142, USA
    Mol Cell 40:310-22. 2010
    ..This review focuses on the key components of the mTOR complex 1 pathway and on how various stresses impinge upon them...
  4. pmc mTORC1 senses lysosomal amino acids through an inside-out mechanism that requires the vacuolar H(+)-ATPase
    Roberto Zoncu
    Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, MA 02142, USA
    Science 334:678-83. 2011
    ..These results identify the v-ATPase as a component of the mTOR pathway and delineate a lysosome-associated machinery for amino acid sensing...
  5. pmc An ATP-competitive mammalian target of rapamycin inhibitor reveals rapamycin-resistant functions of mTORC1
    Carson C Thoreen
    Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA
    J Biol Chem 284:8023-32. 2009
    ..Our findings challenge the assumption that rapamycin completely inhibits mTORC1 and indicate that direct inhibitors of mTORC1 kinase activity may be more successful than rapamycin at inhibiting tumors that depend on mTORC1...
  6. pmc The Rag GTPases bind raptor and mediate amino acid signaling to mTORC1
    Yasemin Sancak
    Whitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology MIT, Nine Cambridge Center, Cambridge, MA 02142, USA
    Science 320:1496-501. 2008
    ..The Rag proteins do not directly stimulate the kinase activity of mTORC1, but, like amino acids, promote the intracellular localization of mTOR to a compartment that also contains its activator Rheb...
  7. ncbi SIN1/MIP1 maintains rictor-mTOR complex integrity and regulates Akt phosphorylation and substrate specificity
    Estela Jacinto
    Department of Physiology and Biophysics, UMDNJ Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA
    Cell 127:125-37. 2006
    ..Our findings reveal that the SIN1-rictor-mTOR function in Akt-Ser473 phosphorylation is required for TORC2 function in cell survival but is dispensable for TORC1 function...
  8. ncbi Ablation in mice of the mTORC components raptor, rictor, or mLST8 reveals that mTORC2 is required for signaling to Akt-FOXO and PKCalpha, but not S6K1
    David A Guertin
    Whitehead Institute for Biomedical Research and Massachusetts Institute of Technology, Department of Biology, Cambridge, Massachusetts 02141, USA
    Dev Cell 11:859-71. 2006
    The mTOR kinase controls cell growth, proliferation, and survival through two distinct multiprotein complexes, mTORC1 and mTORC2...
  9. pmc Inhibition of mTORC1 leads to MAPK pathway activation through a PI3K-dependent feedback loop in human cancer
    Arkaitz Carracedo
    Cancer Genetics Program, Beth Israel Deaconess Cancer Center, Harvard Medical School, Boston, Massachusetts, USA
    J Clin Invest 118:3065-74. 2008
    ....
  10. pmc Ragulator is a GEF for the rag GTPases that signal amino acid levels to mTORC1
    Liron Bar-Peled
    Whitehead Institute for Biomedical Research and Massachusetts Institute of Technology, Department of Biology, Nine Cambridge Center, Cambridge, MA 02142, USA
    Cell 150:1196-208. 2012
    ..Thus, we provide mechanistic insight into how mTORC1 senses amino acids by identifying Ragulator as a guanine nucleotide exchange factor (GEF) for the Rag GTPases...
  11. pmc Activation of a metabolic gene regulatory network downstream of mTOR complex 1
    Katrin Düvel
    Department of Genetics and Complex Diseases, Harvard School of Public Health, Boston, MA 02115, USA
    Mol Cell 39:171-83. 2010
    ..Therefore, in addition to promoting protein synthesis, mTORC1 activates specific bioenergetic and anabolic cellular processes that are likely to contribute to human physiology and disease...
  12. pmc Nutrient-dependent mTORC1 association with the ULK1-Atg13-FIP200 complex required for autophagy
    Nao Hosokawa
    Department of Physiology and Cell Biology, Tokyo Medical and Dental University, Tokyo 113 8519, Japan
    Mol Biol Cell 20:1981-91. 2009
    ..ULK1 is dephosphorylated by rapamycin treatment or starvation. These data suggest that mTORC1 suppresses autophagy through direct regulation of the approximately 3-MDa ULK1-Atg13-FIP200 complex...
  13. pmc BioGRID: a general repository for interaction datasets
    Chris Stark
    Ontario Cancer Institute, Princess Margaret Hospital, 610 University Avenue, Toronto, Ontario, Canada M5G 2M9
    Nucleic Acids Res 34:D535-9. 2006
    ..User-customized graphs with embedded protein, gene and interaction attributes can be constructed with a visualization system called Osprey that is dynamically linked to the BioGRID...
  14. pmc The mTOR-regulated phosphoproteome reveals a mechanism of mTORC1-mediated inhibition of growth factor signaling
    Peggy P Hsu
    Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, MA 02142, USA
    Science 332:1317-22. 2011
    ..Our work clarifies how mTORC1 inhibits growth factor signaling and opens new areas of investigation in mTOR biology...
  15. pmc Phosphoproteomic analysis identifies Grb10 as an mTORC1 substrate that negatively regulates insulin signaling
    Yonghao Yu
    Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    Science 332:1322-6. 2011
    ....
  16. pmc Beclin 1 forms two distinct phosphatidylinositol 3-kinase complexes with mammalian Atg14 and UVRAG
    Eisuke Itakura
    Department of Physiology and Cell Biology, Tokyo Medical and Dental University, Tokyo 113 8519, Japan
    Mol Biol Cell 19:5360-72. 2008
    ..These results suggest that mammalian cells have at least two distinct class III PI3-kinase complexes, which may function in different membrane trafficking pathways...
  17. ncbi mTOR controls mitochondrial oxidative function through a YY1-PGC-1alpha transcriptional complex
    John T Cunningham
    Dana Farber Cancer Institute and Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nature 450:736-40. 2007
    ..These results have important implications for our understanding of how these pathways might be altered in metabolic diseases and cancer...
  18. pmc mTOR complex 1 regulates lipin 1 localization to control the SREBP pathway
    Timothy R Peterson
    Whitehead Institute for Biomedical Research, Koch Center for Integrative Cancer Research at MIT, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA
    Cell 146:408-20. 2011
    ..These findings establish lipin 1 as a key component of the mTORC1-SREBP pathway...
  19. ncbi Leucyl-tRNA synthetase is an intracellular leucine sensor for the mTORC1-signaling pathway
    Jung Min Han
    Medicinal Bioconvergence Research Center, Seoul National University, Seoul 151 742, Republic of Korea
    Cell 149:410-24. 2012
    ..This work demonstrates that LRS is a key mediator for amino acid signaling to mTORC1...
  20. pmc The coordinate regulation of the p53 and mTOR pathways in cells
    Zhaohui Feng
    Cancer Institute of New Jersey, University of Medicine and Dentistry of New Jersey Robert Wood Johnson Medical School, New Brunswick, NJ 08903, USA
    Proc Natl Acad Sci U S A 102:8204-9. 2005
    ..Thus, p53 and mTOR signaling machineries can cross-talk and coordinately regulate cell growth, proliferation, and death...
  21. pmc Bidirectional transport of amino acids regulates mTOR and autophagy
    Paul Nicklin
    Respiratory Diseases Area, Novartis Institutes for BioMedical Research, Novartis Horsham Research Centre, West Sussex, UK
    Cell 136:521-34. 2009
    ..Thus, L-glutamine flux regulates mTOR, translation and autophagy to coordinate cell growth and proliferation...
  22. pmc Active-site inhibitors of mTOR target rapamycin-resistant outputs of mTORC1 and mTORC2
    Morris E Feldman
    Howard Hughes Medical Institute and Department of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, USA
    PLoS Biol 7:e38. 2009
    ..These potent new pharmacological agents complement rapamycin in the study of mTOR and its role in normal physiology and human disease...
  23. pmc A genetic interaction map of RNA-processing factors reveals links between Sem1/Dss1-containing complexes and mRNA export and splicing
    Gwendolyn M Wilmes
    Department of Biochemistry and Biophysics, University of California, San Francisco, 600 16th Street, Genentech Hall, San Francisco, CA 94143 2200, USA
    Mol Cell 32:735-46. 2008
    ..Finally, we show that Csn12 plays a role in pre-mRNA splicing, which is independent of other signalosome components. Thus, Sem1 is involved in three separate and functionally distinct complexes...
  24. pmc A Tumor suppressor complex with GAP activity for the Rag GTPases that signal amino acid sufficiency to mTORC1
    Liron Bar-Peled
    Whitehead Institute for Biomedical Research and Massachusetts Institute of Technology, Department of Biology, Cambridge, MA 02142, USA
    Science 340:1100-6. 2013
    ..Thus, we identify a key negative regulator of the Rag GTPases and reveal that, like other mTORC1 regulators, Rag function can be deregulated in cancer...
  25. pmc Amino acid signalling upstream of mTOR
    Jenna L Jewell
    Department of Pharmacology and Moores Cancer Center, University of California, San Diego, La Jolla, California 92093, USA
    Nat Rev Mol Cell Biol 14:133-9. 2013
    ..Recently, a model has emerged whereby mTORC1 activation occurs at the lysosome and is mediated through an amino acid sensing cascade involving RAG GTPases, Ragulator and vacuolar H(+)-ATPase (v-ATPase)...
  26. ncbi Sch9 is a major target of TORC1 in Saccharomyces cerevisiae
    Jörg Urban
    Department of Molecular Biology, University of Geneva, Geneva, CH 1211, Switzerland
    Mol Cell 26:663-74. 2007
    The Target of Rapamycin (TOR) protein is a Ser/Thr kinase that functions in two distinct multiprotein complexes: TORC1 and TORC2...
  27. pmc ATM signals to TSC2 in the cytoplasm to regulate mTORC1 in response to ROS
    Angela Alexander
    Department of Carcinogenesis, University of Texas MD Anderson Cancer Center, Smithville, TX 78957, USA
    Proc Natl Acad Sci U S A 107:4153-8. 2010
    ....
  28. ncbi The COP9 signalosome: more than a protease
    Ning Wei
    Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06511, USA
    Trends Biochem Sci 33:592-600. 2008
    ..The independent functions of CSN5 (also known as JAB1) add to the complexity of the CSN machinery. Here, we provide an updated view of the structure, functions and regulation of this protein complex...
  29. ncbi mTOR complex 2 (mTORC2) controls hydrophobic motif phosphorylation and activation of serum- and glucocorticoid-induced protein kinase 1 (SGK1)
    Juan M García-Martínez
    MRC Protein Phosphorylation Unit, College of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, UK
    Biochem J 416:375-85. 2008
    ..The results of the present study indicate that NDRG1 phosphorylation represents an excellent biomarker for mTORC2 activity...
  30. pmc A mitochondrial-focused genetic interaction map reveals a scaffold-like complex required for inner membrane organization in mitochondria
    Suzanne Hoppins
    Department of Molecular and Cellular Biology, University of California, Davis, Davis, CA 95616, USA
    J Cell Biol 195:323-40. 2011
    ..We propose that MitOS acts as a conserved mitochondrial skeletal structure that differentiates regions of the inner membrane to establish the normal internal architecture of mitochondria...
  31. ncbi How TCRs bind MHCs, peptides, and coreceptors
    Markus G Rudolph
    Department of Molecular Structural Biology, University of Gottingen, 37077 Gottingen, Germany
    Annu Rev Immunol 24:419-66. 2006
    ..Notwithstanding, the impressive array of self, foreign (microbial), and autoimmune TCR complexes have uncovered the diverse ways in which antigens can be specifically recognized by TCRs...
  32. pmc Essential function of TORC2 in PKC and Akt turn motif phosphorylation, maturation and signalling
    Tsuneo Ikenoue
    Life Sciences Institute, University of Michigan, Ann Arbor, MI, USA
    EMBO J 27:1919-31. 2008
    ..Our study demonstrates that mTORC2 is involved in post-translational processing of PKC by facilitating TM and HM phosphorylation and reveals a novel function of mTORC2 in cellular regulation...
  33. ncbi Activation of mTORC2 by association with the ribosome
    Vittoria Zinzalla
    Biozentrum, University of Basel, CH 4056 Basel, Switzerland
    Cell 144:757-68. 2011
    ..As ribosome content determines growth capacity of a cell, this mechanism of TORC2 regulation ensures that TORC2 is active only in growing cells...
  34. pmc Lysosomal positioning coordinates cellular nutrient responses
    Viktor I Korolchuk
    Department of Medical Genetics, Cambridge Institute for Medical Genetics, Wellcome Trust MRC Building, Hills Road, Cambridge, CB2 0XY, UK
    Nat Cell Biol 13:453-60. 2011
    ..Our findings provide a physiological role for the dynamic state of lysosomal positioning in cells as a coordinator of mTORC1 signalling with autophagic flux...
  35. ncbi The pharmacology of mTOR inhibition
    David A Guertin
    Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, MA 02141, USA
    Sci Signal 2:pe24. 2009
    ..Here, we summarize exciting findings regarding mTOR signaling and the outlook for mTOR inhibitors as tools to study the mTOR pathway and as drugs in the clinic...
  36. pmc Dissecting the role of MPS1 in chromosome biorientation and the spindle checkpoint through the small molecule inhibitor reversine
    Stefano Santaguida
    Department of Experimental Oncology, European Institute of Oncology, I 20139 Milan, Italy
    J Cell Biol 190:73-87. 2010
    ..They also shed light on the relationship between the error correction pathway and the spindle checkpoint and suggest that these processes are coregulated and are likely to share at least a subset of their catalytic machinery...
  37. pmc The TSC1-TSC2 complex is required for proper activation of mTOR complex 2
    Jingxiang Huang
    Department of Genetics and Complex Diseases, Harvard School of Public Health, Boston, Massachusetts 02115, USA
    Mol Cell Biol 28:4104-15. 2008
    ..These data demonstrate that the TSC1-TSC2 complex inhibits mTORC1 and activates mTORC2, which through different mechanisms promotes Akt activation...
  38. pmc Condensins regulate meiotic DNA break distribution, thus crossover frequency, by controlling chromosome structure
    David G Mets
    Howard Hughes Medical Institute, University of California Berkeley, Berkeley, CA 94720 3204, USA
    Cell 139:73-86. 2009
    ....
  39. ncbi Adipose-specific knockout of raptor results in lean mice with enhanced mitochondrial respiration
    Pazit Polak
    Biozentrum, University of Basel, Basel, CH 4056, Switzerland
    Cell Metab 8:399-410. 2008
    ..These results suggest that adipose mTORC1 is a regulator of adipose metabolism and, thereby, controls whole-body energy homeostasis...
  40. pmc Identification of cis-acting sites for condensin loading onto budding yeast chromosomes
    Claudio D'Ambrosio
    Chromosome Segregation Laboratory, Cancer Research UK London Research Institute, London, UK
    Genes Dev 22:2215-27. 2008
    ..This reveals that TFIIIC-binding sites, including tRNA genes, constitute a hitherto unknown chromosomal feature with important implications for chromosome architecture during both interphase and mitosis...
  41. pmc The kinase mTOR regulates the differentiation of helper T cells through the selective activation of signaling by mTORC1 and mTORC2
    Greg M Delgoffe
    Sidney Kimmel Comprehensive Cancer Research Center, Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    Nat Immunol 12:295-303. 2011
    ..These findings define a previously unknown paradigm that links T cell differentiation with selective metabolic signaling pathways...
  42. pmc Targeting mTOR: prospects for mTOR complex 2 inhibitors in cancer therapy
    C A Sparks
    Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA
    Oncogene 29:3733-44. 2010
    ..Here, we summarize exciting new research into the biology of mTORC2 signaling and highlight the current state and future prospects for mTOR-targeted therapy...
  43. ncbi Functional dissection of protein complexes involved in yeast chromosome biology using a genetic interaction map
    Sean R Collins
    Department of Cellular and Molecular Pharmacology, University of California, San Francisco, California 94158, USA
    Nature 446:806-10. 2007
    ..This modification, in turn, enables a ubiquitin ligase complex containing the cullin Rtt101 to ensure genomic integrity during DNA replication...
  44. ncbi The ubiquitin ligase activity in the DDB2 and CSA complexes is differentially regulated by the COP9 signalosome in response to DNA damage
    Regina Groisman
    Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
    Cell 113:357-67. 2003
    ..Knockdown of CSN with RNA interference leads to defects in NER. These results suggest that the distinct UV response of the DDB2 and CSA complexes is involved in diverse mechanisms of NER...
  45. ncbi Skeletal muscle-specific ablation of raptor, but not of rictor, causes metabolic changes and results in muscle dystrophy
    C Florian Bentzinger
    Biozentrum, University of Basel, CH 4056 Basel, Switzerland
    Cell Metab 8:411-24. 2008
    ..mTOR assembles into two distinct multiprotein complexes called mTOR complex 1 (mTORC1) and mTORC2...
  46. pmc Macromolecular crowding and confinement: biochemical, biophysical, and potential physiological consequences
    Huan Xiang Zhou
    Department of Physics and Institute of Molecular Biophysics and School of Computational Science, Florida State University, Tallahassee, Florida 32306, USA
    Annu Rev Biophys 37:375-97. 2008
    ..Theoretical and experimental approaches to the characterization of crowding- and confinement-induced effects in systems approaching the complexity of living organisms are suggested...
  47. pmc mTORC1-mediated cell proliferation, but not cell growth, controlled by the 4E-BPs
    Ryan J O Dowling
    Department of Biochemistry and Goodman Cancer Research Centre, McGill University, Montreal, Quebec H3A 1A3, Canada
    Science 328:1172-6. 2010
    ..Thus, control of cell size and cell cycle progression appear to be independent in mammalian cells, whereas in lower eukaryotes, 4E-BPs influence both cell growth and proliferation...
  48. ncbi PRAS40 is an insulin-regulated inhibitor of the mTORC1 protein kinase
    Yasemin Sancak
    Whitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology, Nine Cambridge Center, Cambridge, MA 02142, USA
    Mol Cell 25:903-15. 2007
    ..We propose that the relative strengths of the rheb- and PRAS40-mediated inputs to mTORC1 set overall pathway activity and that insulin activates mTORC1 through the coordinated regulation of both...
  49. ncbi Tethering factors as organizers of intracellular vesicular traffic
    I Mei Yu
    Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544, USA
    Annu Rev Cell Dev Biol 26:137-56. 2010
    ..The combination of these and other approaches has led to exciting progress toward understanding how these essential nanomachines work...
  50. ncbi Recruitment of condensin to replication origin regions by ParB/SpoOJ promotes chromosome segregation in B. subtilis
    Stephan Gruber
    Centre for Bacterial Cell Biology, Institute for Cell and Molecular Biosciences, Newcastle University, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK
    Cell 137:685-96. 2009
    ..Our results demonstrate a direct functional interaction between two widely conserved systems involved in chromosome replication and segregation...
  51. pmc Feedback on fat: p62-mTORC1-autophagy connections
    Jorge Moscat
    Sanford Burnham Medical Research Institute, 10901 N Torrey Pines Road, La Jolla, CA 92037, USA
    Cell 147:724-7. 2011
    ..Recent in vivo studies explore the molecular basis for metabolic homestasis, showing that p62 links autophagy and mTORC1 activation to regulate adipogenesis and energy control...
  52. pmc MTORC1 functions as a transcriptional regulator of autophagy by preventing nuclear transport of TFEB
    Jose A Martina
    Laboratory of Cell Biology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD USA
    Autophagy 8:903-14. 2012
    ..Our results unveil a novel role for MTORC1 in the maintenance of cellular homeostasis by regulating autophagy at the transcriptional level...
  53. pmc Cse4 is part of an octameric nucleosome in budding yeast
    Raymond Camahort
    Stowers Institute for Medical Research, Kansas City, MO 64110, USA
    Mol Cell 35:794-805. 2009
    ..Taken together, our experimental evidence supports the model that the Cse4 nucleosome is an octamer, containing two copies each of Cse4, H2A, H2B, and H4...
  54. pmc Contrasting roles of condensin I and condensin II in mitotic chromosome formation
    Lydia C Green
    Murdoch Childrens Research Institute, Royal Children s Hospital, Melbourne, Victoria 3052, Australia
    J Cell Sci 125:1591-604. 2012
    ..We conclude that condensin II is required primarily to provide rigidity by establishing an initial chromosome axis around which condensin I can arrange loops of chromatin...
  55. pmc Ku-0063794 is a specific inhibitor of the mammalian target of rapamycin (mTOR)
    Juan M García-Martínez
    MRC Protein Phosphorylation Unit, College of Life Sciences, University of Dundee, Dow Street, Dundee DD15EH, Scotland, UK
    Biochem J 421:29-42. 2009
    ..Our results indicate that Ku-0063794 will be useful in delineating the physiological roles of mTOR and may have utility in treatment of cancers in which this pathway is inappropriately activated...
  56. ncbi Amino acid signaling in TOR activation
    Joungmok Kim
    Department of Pharmacology and Moores Cancer Center, University of California, San Diego, La Jolla, California 92093, USA
    Annu Rev Biochem 80:1001-32. 2011
    ....
  57. ncbi Shugoshin collaborates with protein phosphatase 2A to protect cohesin
    Tomoya S Kitajima
    Laboratory of Chromosome Dynamics, Institute of Molecular and Cellular Biosciences, University of Tokyo, Japan
    Nature 441:46-52. 2006
    ..Thus, we have revealed a conserved mechanism of centromeric protection of eukaryotic chromosomes in mitosis and meiosis...
  58. pmc A double-hexameric MCM2-7 complex is loaded onto origin DNA during licensing of eukaryotic DNA replication
    Cecile Evrin
    DNA replication Group, Medical Research Council Clinical Sciences Centre, Imperial College London, London W12 0NN, United Kingdom
    Proc Natl Acad Sci U S A 106:20240-5. 2009
    ..Our results provide key insights into mechanisms of pre-RC formation and have important implications for understanding the role of the MCM2-7 in establishment of bidirectional replication forks...
  59. ncbi At the heart of the chromosome: SMC proteins in action
    Tatsuya Hirano
    Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, New York 11724, USA
    Nat Rev Mol Cell Biol 7:311-22. 2006
    ..An emerging idea is that SMC proteins use a diverse array of intramolecular and intermolecular protein-protein interactions to actively fold, tether and manipulate DNA strands...
  60. pmc Condensin and cohesin complexity: the expanding repertoire of functions
    Andrew J Wood
    Howard Hughes Medical Institute and Department of Molecular and Cell Biology, University of California Berkeley, Berkeley, California 94720 3204, USA
    Nat Rev Genet 11:391-404. 2010
    ..Emerging data are expanding the range of processes in which condensin and cohesin are known to participate and are enhancing our knowledge of how chromosome architecture is regulated to influence numerous cellular functions...
  61. pmc Architecture of the RNA polymerase II-TFIIF complex revealed by cross-linking and mass spectrometry
    Zhuo Angel Chen
    Wellcome Trust Centre for Cell Biology, Institute of Cell Biology, The University of Edinburgh, Edinburgh, UK
    EMBO J 29:717-26. 2010
    ..This work establishes cross-linking/MS as an integrated structure analysis tool for large multi-protein complexes...
  62. pmc The efficacy of the novel dual PI3-kinase/mTOR inhibitor NVP-BEZ235 compared with rapamycin in renal cell carcinoma
    Daniel C Cho
    Division of Hematology and Oncology, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA
    Clin Cancer Res 16:3628-38. 2010
    ....
  63. pmc TBC1D7 is a third subunit of the TSC1-TSC2 complex upstream of mTORC1
    Christian C Dibble
    Department of Genetics and Complex Diseases, Harvard School of Public Health, Boston, MA 02115, USA
    Mol Cell 47:535-46. 2012
    ..Like the other TSC-TBC components, TBC1D7 knockdown results in increased mTORC1 signaling, delayed induction of autophagy, and enhanced cell growth under poor growth conditions...
  64. ncbi Condensin association with histone H2A shapes mitotic chromosomes
    Kenji Tada
    Laboratory of Chromosome Dynamics, Institute of Molecular and Cellular Biosciences, University of Tokyo, Yayoi, Tokyo 113 0032, Japan
    Nature 474:477-83. 2011
    ..Our results elucidate the molecular basis for the spatiotemporal regulation of mitotic chromosome architecture, which is crucial for chromosome partitioning...
  65. ncbi Proteome organization in a genome-reduced bacterium
    Sebastian Kühner
    European Molecular Biology Laboratory, Meyerhofstrasse 1, D 69117 Heidelberg, Germany
    Science 326:1235-40. 2009
    ..The data set provides a blueprint of the minimal cellular machinery required for life...
  66. ncbi TPP1 is a homologue of ciliate TEBP-beta and interacts with POT1 to recruit telomerase
    Huawei Xin
    Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA
    Nature 445:559-62. 2007
    ....
  67. pmc PatchDock and SymmDock: servers for rigid and symmetric docking
    Dina Schneidman-Duhovny
    School of Computer Science, Raymond and Beverly Sackler Faculty of Exact Sciences, Tel Aviv University, Tel Aviv 69978, Israel
    Nucleic Acids Res 33:W363-7. 2005
    ..The services are available at http://bioinfo3d.cs.tau.ac.il. The methods behind the servers are very efficient, allowing large-scale docking experiments...
  68. ncbi FireDock: fast interaction refinement in molecular docking
    Nelly Andrusier
    School of Computer Science, Raymond and Beverly Sackler Faculty of Exact Sciences, Tel Aviv University, Tel Aviv 69978, Israel
    Proteins 69:139-59. 2007
    ..The method is available at http://bioinfo3d.cs.tau.ac.il/FireDock/...
  69. ncbi A protein interaction network for pluripotency of embryonic stem cells
    Jianlong Wang
    Division of Hematology Oncology, Children s Hospital and Dana Farber Cancer Institute, Harvard Medical School, Harvard Stem Cell Institute, Boston, Massachusetts 02115, USA
    Nature 444:364-8. 2006
    ..This tight protein network seems to function as a cellular module dedicated to pluripotency...
  70. pmc HexServer: an FFT-based protein docking server powered by graphics processors
    Gary Macindoe
    Department of Computing Science, Lillybank Gardens, University of Glasgow, G12 8QQ Scotland, UK
    Nucleic Acids Res 38:W445-9. 2010
    ..The server is publicly available and does not require any registration or identification by the user...
  71. pmc Global functional atlas of Escherichia coli encompassing previously uncharacterized proteins
    Pingzhao Hu
    Banting and Best Department of Medical Research, Terrence Donnelly Center for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario, Canada
    PLoS Biol 7:e96. 2009
    ..Clustering of the respective probabilistic networks revealed putative orphan membership in discrete multiprotein complexes and functional modules together with annotated gene products, whereas a machine-learning strategy based on ..
  72. ncbi Identification of a multicomponent complex required for outer membrane biogenesis in Escherichia coli
    Tao Wu
    Department of Chemistry, Princeton University, Princeton, New Jersey 08544, USA
    Cell 121:235-45. 2005
    ..These genetic interactions suggest a role for YfgL, one of the lipoprotein components of the protein assembly complex, in a homeostatic control mechanism that coordinates the overall OM assembly process...
  73. pmc mTOR Ser-2481 autophosphorylation monitors mTORC-specific catalytic activity and clarifies rapamycin mechanism of action
    Ghada A Soliman
    Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, Michigan 48109 2200, USA
    J Biol Chem 285:7866-79. 2010
    The mammalian target of rapamycin (mTOR) Ser/Thr kinase signals in at least two multiprotein complexes distinguished by their different partners and sensitivities to rapamycin...
  74. pmc GRAMM-X public web server for protein-protein docking
    Andrey Tovchigrechko
    Center for Bioinformatics, The University of Kansas, 2030 Becker Drive, Lawrence, KS 66047, USA
    Nucleic Acids Res 34:W310-4. 2006
    ..Docking problems submitted to GRAMM-X server are processed by a 320 processor Linux cluster. The server was extensively tested by benchmarking, several months of public use, and participation in the CAPRI server track...
  75. ncbi Dual inhibition of PI3K and mTORC1/2 signaling by NVP-BEZ235 as a new therapeutic strategy for acute myeloid leukemia
    Nicolas Chapuis
    Institut Cochin, Universite Paris Descartes, CNRS UMR8104 INSERM U1016 Service d Hématologie Biologique, Hopital Cochin, AP HP, Paris, France
    Clin Cancer Res 16:5424-35. 2010
    ..We therefore tested, in this study, the antileukemic activity of the dual PI3K/mTOR ATP-competitive inhibitor NVP-BEZ235 compound (Novartis)...
  76. ncbi Beyond rapalog therapy: preclinical pharmacology and antitumor activity of WYE-125132, an ATP-competitive and specific inhibitor of mTORC1 and mTORC2
    Ker Yu
    Discovery Oncology and Discovery Medicinal Chemistry, Wyeth Research, Pearl River, New York 10965, USA
    Cancer Res 70:621-31. 2010
    ....
  77. pmc Saccharomyces cerevisiae Mre11/Rad50/Xrs2 and Ku proteins regulate association of Exo1 and Dna2 with DNA breaks
    Eun Yong Shim
    Department of Molecular Medicine, Institute of Biotechnology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
    EMBO J 29:3370-80. 2010
    ..However, Mre11 nuclease activity is essential for resection in the absence of extensive resection enzymes. The results provide new insights into how MRX catalyses end resection and recombination initiation...
  78. ncbi Chromosome alignment and transvection are antagonized by condensin II
    Tom A Hartl
    Department of Molecular and Cellular Biology, University of Arizona, 1007 East Lowell Street, Tucson, AZ 85721 0106, USA
    Science 322:1384-7. 2008
    ..We propose that condensin II restricts trans-chromosomal interactions that affect transcription through its ability to spatially separate aligned interphase chromosomes...
  79. pmc In vivo protein architecture of the eukaryotic kinetochore with nanometer scale accuracy
    Ajit P Joglekar
    Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
    Curr Biol 19:694-9. 2009
    ....
  80. ncbi Progress and challenges in predicting protein-protein interaction sites
    Iakes Ezkurdia
    Centro Nacional de Biotechnolgia, Spanish National Cancer Research Centre CNIO, Madrid, Spain
    Brief Bioinform 10:233-46. 2009
    ..We provide suggestions for effective feature selection, and make it clear that community standards for testing, training and performance measures are necessary for progress in the field...
  81. pmc Deconstructing the cadherin-catenin-actin complex
    Soichiro Yamada
    Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, USA
    Cell 123:889-901. 2005
    ..These results suggest that the linkage between the cadherin-catenin complex and actin filaments is more dynamic than previously appreciated...
  82. ncbi Proteome survey reveals modularity of the yeast cell machinery
    Anne Claude Gavin
    Cellzome AG, Meyerhofstrasse 1, 69117 Heidelberg, Germany
    Nature 440:631-6. 2006
    ..This study provides the largest collection of physically determined eukaryotic cellular machines so far and a platform for biological data integration and modelling...
  83. pmc Characterization of the role of COP9 signalosome in regulating cullin E3 ubiquitin ligase activity
    Yin Yin Choo
    Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, 117597 Singapore
    Mol Biol Cell 22:4706-15. 2011
    ..The deneddylating activity of CSN would subsequently promote its own dissociation to allow progression through the CRL activation cycle...
  84. ncbi The Mcm2-7 complex has in vitro helicase activity
    Matthew L Bochman
    Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA 15260, USA
    Mol Cell 31:287-93. 2008
    ..Our results show that purified Mcm2-7 acts as a helicase, provides functional evidence of a Mcm2/5 gate, and lays the foundation for future mechanistic studies of this critical factor...
  85. ncbi The APP intracellular domain forms nuclear multiprotein complexes and regulates the transcription of its own precursor
    Ruth C von Rotz
    Division of Psychiatry Research, University of Zurich, August Forel Str 1, 8008 Zurich, Switzerland
    J Cell Sci 117:4435-48. 2004
    ..These data establish a role for APP in nuclear signaling, and they suggest that therapeutic strategies designed to modulate the cleavage of APP affect AICD-dependent signaling...
  86. ncbi The mitochondrial inner membrane protein mitofilin exists as a complex with SAM50, metaxins 1 and 2, coiled-coil-helix coiled-coil-helix domain-containing protein 3 and 6 and DnaJC11
    Jing Xie
    Institute of Molecular Biology, University of Oregon, Eugene, OR 97403, USA
    FEBS Lett 581:3545-9. 2007
    ....
  87. pmc Condensin regulates the stiffness of vertebrate centromeres
    Susana A Ribeiro
    Wellcome Trust Centre for Cell Biology, Institute of Cell and Molecular Biology, University of Edinburgh, Edinburgh EH9 3JR, United Kingdom
    Mol Biol Cell 20:2371-80. 2009
    ..Loss of stiffness caused by condensin-depletion produces abnormal uncoordinated sister kinetochore movements, leads to an increase in Mad2(+) kinetochores near the metaphase plate and delays anaphase onset...
  88. pmc ANCHOR: a web server and database for analysis of protein-protein interaction binding pockets for drug discovery
    Lidio M C Meireles
    Department of Computational Biology, University of Pittsburgh, Pittsburgh, PA 15261, USA
    Nucleic Acids Res 38:W407-11. 2010
    ..ANCHOR web server and database are freely available at http://structure.pitt.edu/anchor...
  89. pmc mTORC1 promotes survival through translational control of Mcl-1
    John R Mills
    Department of Biochemistry, McGill University, Montreal, QC, Canada H3G 1Y6
    Proc Natl Acad Sci U S A 105:10853-8. 2008
    ..Our results indicate that the extent by which rapamycin can modulate expression of Mcl-1 is an important feature of the rapamycin response...
  90. ncbi Structure of Atg5.Atg16, a complex essential for autophagy
    Minako Matsushita
    Department of Structural Biology, Graduate School of Pharmaceutical Sciences, Hokkaido University, N 21, W 11, Kita ku, Sapporo 001 0021, Japan
    J Biol Chem 282:6763-72. 2007
    ..These results taken together suggest that the direct interaction between Atg5 and Atg16 is crucial to the performance of their roles in autophagy...
  91. ncbi Prediction of sequence-dependent and mutational effects on the aggregation of peptides and proteins
    Ana Maria Fernandez-Escamilla
    Nat Biotechnol 22:1302-6. 2004
    ..Furthermore, the algorithm opens the door to a fully automated, sequence-based design strategy to improve the aggregation properties of proteins of scientific or industrial interest...
  92. pmc Making the best of the loose ends: Mre11/Rad50 complexes and Sae2 promote DNA double-strand break resection
    Tanya T Paull
    The Howard Hughes Medical Institute, The Department of Molecular Genetics and Microbiology, The University of Texas at Austin, Austin, TX 78712, USA
    DNA Repair (Amst) 9:1283-91. 2010
    ....
  93. pmc Mps1 directs the assembly of Cdc20 inhibitory complexes during interphase and mitosis to control M phase timing and spindle checkpoint signaling
    John Maciejowski
    Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
    J Cell Biol 190:89-100. 2010
    ....
  94. ncbi How proteins get in touch: interface prediction in the study of biomolecular complexes
    Sjoerd J de Vries
    Bijvoet Center for Biomolecular Research, Science Faculty, Utrecht University, 3584CH, Utrecht, The Netherlands
    Curr Protein Pept Sci 9:394-406. 2008
    ..The focus is mainly on protein-protein interface prediction, although most issues are also valid for other kinds of interface prediction...
  95. pmc Structure of the LKB1-STRAD-MO25 complex reveals an allosteric mechanism of kinase activation
    Elton Zeqiraj
    Division of Molecular Microbiology, College of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland
    Science 326:1707-11. 2009
    ..The structure also reveals how mutations found in Peutz-Jeghers syndrome and in various sporadic cancers impair LKB1 function...
  96. pmc Sustained Mps1 activity is required in mitosis to recruit O-Mad2 to the Mad1-C-Mad2 core complex
    Laura Hewitt
    Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, England, UK
    J Cell Biol 190:25-34. 2010
    ..We propose a model whereby Mps1 transphosphorylation results in its release from kinetochores, thus facilitating recruitment of O-Mad2 and CENP-E and thereby simultaneously promoting checkpoint signaling and chromosome congression...
  97. pmc Ku prevents Exo1 and Sgs1-dependent resection of DNA ends in the absence of a functional MRX complex or Sae2
    Eleni P Mimitou
    Department of Microbiology and Immunology, Columbia University Medical Center, New York, NY, USA
    EMBO J 29:3358-69. 2010
    ..Finally, we show that the presence of Ku exacerbates DNA end-processing defects established in the sae2Δ sgs1Δ mutant, leading to its lethality...
  98. pmc A pathway for phagosome maturation during engulfment of apoptotic cells
    Jason M Kinchen
    Beirne Carter Center for Immunology Research, University of Virginia, Charlottesville, VA 22908, USA
    Nat Cell Biol 10:556-66. 2008
    ..Finally, we have also identified a previously undescribed biochemical complex containing Vps34, dynamin and Rab5(GDP), thus providing a mechanism for Rab5 recruitment to the nascent phagosome...
  99. pmc Functional reconstitution of ESCRT-III assembly and disassembly
    Suraj Saksena
    Weill Institute for Cell and Molecular Biology and Department of Molecular Biology and Genetics, Weill Hall, Cornell University, Ithaca, NY 14853, USA
    Cell 136:97-109. 2009
    ..Furthermore, using an in vitro disassembly assay, we directly demonstrate that Vps24 and Vps2 function as adaptors in the ATP-dependent membrane disassembly of the ESCRT-III complex by recruiting the AAA ATPase Vps4...
  100. pmc Direct binding of Cenp-C to the Mis12 complex joins the inner and outer kinetochore
    Emanuela Screpanti
    Department of Experimental Oncology, European Institute of Oncology, Milan, Italy
    Curr Biol 21:391-8. 2011
    ..Our studies unveil a crucial and likely universal link between the inner and outer kinetochore...
  101. pmc Human chromokinesin KIF4A functions in chromosome condensation and segregation
    Manjari Mazumdar
    National Cancer Institute, National Institutes of Health, Bldg 41, Rm B 507, 41 Library Dr, Bethesda, MD 20892, USA
    J Cell Biol 166:613-20. 2004
    ..Our results provide functional evidence that human KIF4A is a novel component of the chromosome condensation and segregation machinery functioning in multiple steps of mitotic division...

Research Grants63

  1. Membrane-associated PDE3-binding proteins in human myocardium
    Matthew A Movsesian; Fiscal Year: 2013
    ..Recent experiments, however, indicate that membrane-associated PDE3 isoforms integrate into multiprotein complexes with other membrane-associated proteins, providing a mechanism through which they can selectively regulate ..
  2. FUNCTION OF THE KINETOPLAST IN THE HEMOFLAGELLATES
    Larry Simpson; Fiscal Year: 2013
    ..Several additional multiprotein complexes which may be involved in RNA regulation interact with the RECC via RNA linkers...
  3. Receptor Tyrosine Kinase Sorting and Transactivation in Endosomes
    MARK LINDSAY GRIMES; Fiscal Year: 2010
    ..Specifically, we hypothesize that multiprotein complexes of receptors and their effectors in endosomes play a role in receptor crosstalk, and that receptor ..
  4. Roles of rictor in mTOR signaling, differentiation &immune memory via Akt &PKC
    Mark R Boothby; Fiscal Year: 2013
    ..but recent findings show that mTOR functions through at least two mutually exclusive classes of multiprotein complexes. The first, mTORC1, is rapamycin-sensitive and regulates aspects of protein translation and cellular ..
  5. Epigenetic regulation of HIV latency
    ERIC M VERDIN; Fiscal Year: 2013
    ..chromatin immunoprecipitation and shRNA-mediated interference to explore the roles in HIV latency of the multiprotein complexes that are recruited to methylated DNA: NuRD/MBD2, SWI/SNF/Sin3/MeCP2 and the SUV39H1/HP1/MBD1 complexes...
  6. Structure and Function of the SAGA Deubiquitinating Module
    Cynthia Wolberger; Fiscal Year: 2013
    ..These biochemical events are orchestrated by large multiprotein complexes containing histone-modifying enzymes, along with other subunits that control enzyme activity, recognize ..
  7. Stochastic Models of Cell Cycle Regulation in Eukaryotes
    John J Tyson; Fiscal Year: 2013
    ..methods are needed to reliably track the interactions of all the relevant genes, mRNAs, proteins, and multiprotein complexes. Deterministic models (ordinary differential equations) are adequate for understanding the average ..
  8. Barrier Insulators in Erythropoiesis
    Patrick G Gallagher; Fiscal Year: 2013
    ..The goal of the third aim is to characterize the multiprotein complexes associated with barrier insulators in erythroid cells, addressing the hypothesis that these complexes ..
  9. Peptidoglycan synthesis during sporulation
    Jonathan Dworkin; Fiscal Year: 2012
    ..protein mediates translocation of the peptidoglycan precursor during sporulation;(2) to characterize the multiprotein complexes including the protein that mediate cell wall synthesis;and (3) to examine the subcellular localization of ..
  10. Nucleoprotein Structures at Telomeres and Sites of DNA Damage
    Jack D Griffith; Fiscal Year: 2013
    ..New EM tagging methods that identify proteins in multiprotein complexes have been developed and will be applied along with new ultra-gentle preparative methods, cryoEM and single ..
  11. Repair of Oxidized Bases in Mammalian Genomes
    Sankar Mitra; Fiscal Year: 2012
    ..Formation of multiprotein complexes in response to radiation and oxidative stress, which may also be affected by covalent modification of ..
  12. Colon Cell Differentiation: NAB and MUC2 Gene Expression
    Anna Velcich; Fiscal Year: 2009
    ..relevant sites, and the transcription factors and co-factors that may participate in the formation of multiprotein complexes upon interaction with SP1 and SP3 as a function of MUC2 repression. 5...
  13. Chaperone-Enabled studies of epigenetic regulation enzymes
    Anthony A Kossiakoff; Fiscal Year: 2013
    ..determination of individual enzymes in multiple conformational states, enzyme-substrate complexes and multiprotein complexes. A unique strength of our approach is that we will provide crystallization chaperones and the information ..
  14. Intervention models for thyroid proliferative disease using a bioactive food comp
    Raj K Tiwari; Fiscal Year: 2013
    ..II. Examine the regulation of the activation of Akt and ERK pathway in BM-EPC and TPD cells by E2-ER multiprotein complexes and the possible molecular intervention targets of DIM. III...
  15. GABA(A) RECEPTOR TRAFFICKING AND EPILEPTOGENESIS
    Marco I Gonzalez; Fiscal Year: 2013
    ..Finally, native GABAAR multiprotein complexes will be isolated from control and epileptic rats and their components identified using a proteomic ..
  16. Structural mechanisms of Mcm10 in DNA replication
    Brandt F Eichman; Fiscal Year: 2010
    ..Replication initiation involves a choreographed assembly of several dynamic multiprotein complexes, which must recognize and unwind DNA at origins of replication, interpret checkpoint signals, and ..
  17. ION CHANNEL REGULATION AND MODULATION IN CARDIAC MUSCLE
    Jeanne M Nerbonne; Fiscal Year: 2013
    ....
  18. Novel Pattern Specific Isotopic Labeling of Aromatic Amino Acids
    Robert McFeeters; Fiscal Year: 2010
    ..To demonstrate the utility of the new reagents and to establish guidelines for their implementation, the researchers will apply the newly developed, inexpensive reagents to multiple recombinant systems. ..
  19. Cyclic AMP Mediation of Epithelial Cell Function
    JAMES RICHARD GOLDENRING; Fiscal Year: 2012
    ..The challenge of studying these large anchored multiprotein complexes is to discern the role of specific coordinated complexes in the regulation of intracellular processes...
  20. NOD-Like Receptor Signaling is Critical to Secondhand Smoke-Induced Immunity and
    Sanjay Batra; Fiscal Year: 2013
    ..Some NLRs are a part of multiprotein complexes known as inflammasomes which lead to the activation of caspase-1 and subsequent production of IL-1[..
  21. mTOR in Growth and Protection of Hypertrophying Myocardium
    Dhandapani Kuppuswamy; Fiscal Year: 2012
    ..indicate that mTOR has both rapamycin-insensitive and sensitive kinase functions by forming two distinct multiprotein complexes: mTORC2, which promotes removal of deleterious cellular proteins that are potential targets of Akt (..
  22. Olfactory Singaling, Cilia, and Sensory Disorders
    JEFFREY MARTENS; Fiscal Year: 2012
    ..of the ciliary transport pathway which orchestrate the trafficking of signaling proteins by assembly of multiprotein complexes in the basal body/cilia compartment...
  23. Role of 11q23 Chromosome Abnormalities in the Causation of Acute Leukemia
    Carlo M Croce; Fiscal Year: 2013
    ..methodologies, including genome-wide location analysis, genome-wide expression profiling, purification of multiprotein complexes and characterization of their components by mass spectroscopy, assaying microRNAs processing in vitro and ..
  24. Analysis of Radiomitigative Cell Signaling
    Gabor J Tigyi; Fiscal Year: 2012
    ..The objective of this grant application is to elucidate the an- tiapoptotic mechanism of action unique to the LPA2 receptor subtype ..
  25. Mechanisms of Inflammasome Inhibition by Salmonella
    Igor E Brodsky; Fiscal Year: 2013
    ..Members of the cytosolic Nod-like Receptor (NLR) protein family direct assembly of multiprotein complexes termed 'inflammasomes'in response to detection of microbial products in the cytosol or ..
  26. YK-4-279 specifically targets ETS family fusion-protein cancers in clinical trial
    Jeffrey A Toretsky; Fiscal Year: 2010
    ..Our approach recognizes that cancer cell transcription is a highly-balanced process requiring multiprotein complexes for mRNA synthesis and regulation...
  27. Inactivation of LSD1 as a possible treatment for sickle cell disease
    James Douglas Engel; Fiscal Year: 2013
    ..subunit composition of DRED, which is composed of at least four distinct epigenetic modifier co-repressor multiprotein complexes. One of the modifying enzymes is LSD1, a monoamine oxidase that removes activating chromatin signatures, ..
  28. TOR kinase inhibitors for leukemia therapy: mechanisms of action and resistance
    David A Fruman; Fiscal Year: 2013
    ..these compounds fully inhibit the TOR enzyme when it is present in TORC1 or TORC2, two distinct multiprotein complexes. Compared to rapamycin, an allosteric inhibitor, active-site TOR inhibitors have a broader effect on key ..
  29. Epigenetic control of multipotent cardiac progenitor cell differentiation
    Zhong Wang; Fiscal Year: 2013
    ..ATP-dependent chromatin remodelers mediate one critical epigenetic mechanism. These large multiprotein complexes open up chromatin to modulate transcription factor access to DNA...
  30. KV CHANNEL FUNCTIONING IN MACROMOLECULAR COMPLEXES
    Jeanne M Nerbonne; Fiscal Year: 2010
    ....
  31. Regulation of RUNX1 Multiprotein Complex Formation during Hematopoiesis
    Alan B Cantor; Fiscal Year: 2013
    ..Our prior work and that of others in the field indicates that RUNX1 assembles into large dynamic multiprotein complexes that modulate its activity...
  32. Role of mTOR, a Component of the Akt Pathway, in Regulating Cardiac Function
    Kirk U Knowlton; Fiscal Year: 2013
    ..mRNA translation in its dephosphorylated form and a major substrate of TORC-1, one of the two mTOR kinase multiprotein complexes. We found that acumulation of dephosphorylated 4E-BP1 is a feature of HF of diverse etiologies, and thus ..
  33. E2F7 &E2F8 in the control of transcription and cellular proliferation
    GUSTAVO WALTER LEONE; Fiscal Year: 2012
    ..This work will elucida the individual and combinatorial contributions made by these two highly related family members towards the overall understanding of E2F transcriptional activity. Project Description Page 6 ..
  34. SMOOTH MUSCLE MECHANISMS IN DYNAMIC AIRWAY PROPERTIES
    Susan J Gunst; Fiscal Year: 2013
    ..The adhesion junctions that connect cells within tissues to the extracellular matrix are composed of large multiprotein complexes termed "adhesomes"...
  35. NLR Regulation of Gastrointestinal Inflammation and Tumorigenesis
    Irving C Allen; Fiscal Year: 2013
    ..One subset of NLR family members have been shown to form multiprotein complexes, defined as inflammasomes, which can be further characterized by the specific NLR involved in formation...
  36. Specificity and in vivo function of the Naip/Nlrc4 inflammasomes
    Russell E Vance; Fiscal Year: 2013
    ..Inflammasomes comprise a family of multiprotein complexes that assemble in the cytosol in response to noxious and infectious stimuli...
  37. Multicolor TIRF microscope for studying mitotic spindle components at the single
    Charles L Asbury; Fiscal Year: 2010
    ..microscope capable of simultaneously recording interactions between individual protein molecules, multiprotein complexes, and dynamic microtubule filaments...
  38. K+ channel complexes: assembly, trafficking and function
    William R Kobertz; Fiscal Year: 2013
    ....
  39. Regulation of a deubiquitinating enzyme in proteolysis and chromatin remodeling
    Tingting Yao; Fiscal Year: 2013
    ..DUB conserved from fission yeast to man, is partitioned between two structurally and functionally distinct multiprotein complexes, the proteasome regulatory particle (RP) and the human Ino80 chromatin- remodeling complex (hINO80), and ..
  40. MOLECULAR PATHOGENESIS OF HYPOPHOSPHATEMIC RICKETS
    Suzanne M Jan De Beur; Fiscal Year: 2011
    ..of NaPi-lla trafficking, activation of the cell signaling pathways and the assembly of NHERF-1 dependent multiprotein complexes that integrate signaling and NaPi-lla membrane localization...
  41. Identification of novel co-factors for HIV Tat and Rev as therapeutic targets
    Andrew P Rice; Fiscal Year: 2013
    ..Nearly all processes in cells are carried out by multiprotein complexes which are thought to be the minimal functional unit...
  42. ROLE OF CELLULAR PROTEINS IN HPV TRANSCRIPTION
    Cheng Ming Chiang; Fiscal Year: 2004
    ..general transcription factors and cofactors (TBP, TFIIB, TFIIE, TFIIF, and PC4) and epitope-tagged multiprotein complexes (TFIID, TFIIH, and RNA polymerase II) suggests that components of the general transcription machinery are ..
  43. MOLECULAR MECHANISM OF THE CYTOPLAMIC DYNEIN-DYNACTIN MOTOR COMPLEX
    Arne Gennerich; Fiscal Year: 2013
    ..for recombinant full-length dynein and dynactin, to produce stable wildtype and mutant versions of both multiprotein complexes. Using these biochemical tools and multicolor single-molecule fluorescence and optical tweezers methods, ..
  44. GENETIC CONTROL OF DEVELOPMENT
    JAMES ALFRED HOCH; Fiscal Year: 2013
    ..Protein:protein association in heterologous multiprotein complexes is one means for sharing information between processes and for amalgamating enzymes of biosynthetic ..
  45. Functional elucidation of BRCA1-containing complexes
    Ramin Shiekhattar; Fiscal Year: 2010
    Our laboratory is focused on the function of nuclear multiprotein complexes containing BRCA1. We have used biochemical methods to isolate and functionally characterize two distinct BRCA1-containing complexes termed BRCC and BRCA1-BACH1...
  46. Three-Dimensional Imaging of Whole Cells by Using X-ray Diffraction Microscopy
    Jianwei Miao; Fiscal Year: 2010
    ..the 3D intracellular structure of frozen-hydrated cells at a resolution of 10 nm;and 4) localize specific multiprotein complexes in Caulobacter and yeast...
  47. Chemical tools for profiling and visualizing functioning ion channel complexes
    WILLIAM R contact KOBERTZ; Fiscal Year: 2010
    ..This project describes the development of a novel set of reagents to probe the structure, function and cellular localization of healthy and diseased ion channel complexes. ..
  48. Proteomic Study of Megakaryocyte Transcriptional Control
    Alan Cantor; Fiscal Year: 2007
    ..studies using gel filtration chromatography indicate that GATA-1 participates in at least two stable multiprotein complexes of about 360 and 230 kDa in the L8057 murine megakaryocytic cell line (molecular mass of GATA-1 alone is ..
  49. Visualization of Combinatorial Epigenetic Marks and Complexes in Animals Using Fl
    Tom Kerppola; Fiscal Year: 2013
    ..Epigenetic states consist of combinations of molecular marks in conjunction with multiprotein complexes that act on those marks...
  50. Targeting TORC2 in Multiple Myeloma
    Alan K Lichtenstein; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): The mTOR kinase functions in two multiprotein complexes, TORC1 and TORC2, and is a tumor promoting protein...
  51. Structure and function of protein kinase/PP2A complexes
    Brian Wadzinski; Fiscal Year: 2007
    ..that regulation of kinases and phosphatases involves their association with specific cellular proteins in multiprotein complexes. Published findings from the applicant's laboratory have revealed that specific protein serine/..
  52. Structural Diversity of RNA-Binding Proteins
    Alan Frankel; Fiscal Year: 2004
    ..contribute to RNA-binding specificity in different contexts, from small peptide-RNA complexes to large multiprotein complexes, we now propose to: 1) use combinatorial strategies to more precisely define molecular details of amino ..
  53. Structural Study of Semaphorins, Neuropilins and Plexins
    Dimitar Nikolov; Fiscal Year: 2009
    ..The semaphorin receptors are multiprotein complexes, which include a plexin molecule serving as the signal-transducing subunit...
  54. A new genetic tool for analyzing protocadherin diversity in mice
    XIAOZHONG ALEC WANG; Fiscal Year: 2013
    ..This line of investigation will advance our understanding of molecular diversity underlying the precision of neural circuitry in the brain. ..
  55. Functional Proteomic Analysis of Cardiac Mitochondria
    Peipei Ping; Fiscal Year: 2005
    ..Recent studies have demonstrated that proteins are organized as multiprotein complexes within functional sub- 3roteomes...
  56. TRANSCRIPTIONAL REGULATION OF HTLV GENE EXPRESSION
    SUSAN MARRIOTT; Fiscal Year: 2006
    ..its interactions with cellular transcription factors and coactivators result in the assembly of large multiprotein complexes that play a central role in the ability of Tax to regulate transcription of a select subset of available ..
  57. Tax Transactivation in the Context of Chromatin
    Paul Laybourn; Fiscal Year: 2005
    ..Tax is critical to the viral life cycle, as it activates HTLV-I transcription following the assembly of multiprotein complexes in the transcriptional control region of the virus...
  58. Chemical Screen of TOR pathway GFP fusion proteins in S. cerevisiae
    Margaret Werner Washburne; Fiscal Year: 2009
    ..The target of rapamycin, TOR, is an essential ser/thr protein kinase that functions in two distinct multiprotein complexes, TOR complexes 1 and 2...
  59. CRYSTALLOGRAPHIC STUDIES OF TROPONIN C
    Muttaiya Sundaralingam; Fiscal Year: 1990
    ..only three calcium ions) for possible x-ray structure determination; carry out crystallization of the multiprotein complexes the whole troponin C + I + T, and C + I...
  60. Proteomic /Genetic Approaches to Monoamine Transporters
    Gonzalo Torres; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable] [unreadable]..
  61. REGULATION OF THE PLASMA MEMBRANE CALCIUM ATPASE
    EMANUEL STREHLER; Fiscal Year: 2002
    ..project will explore the hypothesis that specific plasma membrane Ca2+ ATPase isoforms are targeted to multiprotein complexes where they associate with other receptors, transporters, channels, and signaling molecules to form "units ..
  62. Single molecule nucleic acid enzymology
    KEVIN RANEY; Fiscal Year: 2009
    ..molecule level in order to test the cooperative inchworm mechanism and lay the groundwork for studying multiprotein complexes on DNA...
  63. OPTIMA XL-A ANALYTICAL ULTRACENTRIFUGE SYSTEM
    Marc Kirschner; Fiscal Year: 1992
    ..Oligomerization of Tubulins and Cell Cycle Proteins;" Bruce Alberts ("Isolation and Characterization of Multiprotein Complexes"); Tim Mitchison ("Microtubule Dynamics and Mitotic Mechanism"); and Alexander (Sandy) Johnson ("..