f box proteins

Summary

Summary: A family of proteins that share the F-BOX MOTIF and are involved in protein-protein interactions. They play an important role in process of protein ubiquition by associating with a variety of substrates and then associating into SCF UBIQUITIN LIGASE complexes. They are held in the ubiquitin-ligase complex via binding to SKP DOMAIN PROTEINS.

Top Publications

  1. pmc The Fbw7 tumor suppressor regulates glycogen synthase kinase 3 phosphorylation-dependent c-Myc protein degradation
    Markus Welcker
    Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
    Proc Natl Acad Sci U S A 101:9085-90. 2004
  2. pmc Systematic analysis and nomenclature of mammalian F-box proteins
    Jianping Jin
    Genes Dev 18:2573-80. 2004
  3. ncbi Phosphorylation-dependent ubiquitination of cyclin E by the SCFFbw7 ubiquitin ligase
    D M Koepp
    Department of Biochemistry and Molecular Biology, Howard Hughes Medical Institute, Baylor College of Medicine, Houston, TX, 77030, USA
    Science 294:173-7. 2001
  4. pmc The SCFFBW7 ubiquitin ligase complex as a tumor suppressor in T cell leukemia
    Benjamin J Thompson
    Department of Pathology, New York University School of Medicine, New York, NY 10016, USA
    J Exp Med 204:1825-35. 2007
  5. ncbi Plant development is regulated by a family of auxin receptor F box proteins
    Nihal Dharmasiri
    Department of Biology, Indiana University, Bloomington, Indiana 47405, USA
    Dev Cell 9:109-19. 2005
  6. ncbi SKP1 connects cell cycle regulators to the ubiquitin proteolysis machinery through a novel motif, the F-box
    C Bai
    Howard Hughes Medical Institute, Baylor College of Medicine, Houston, Texas 77030, USA
    Cell 86:263-74. 1996
  7. ncbi Structure of a Fbw7-Skp1-cyclin E complex: multisite-phosphorylated substrate recognition by SCF ubiquitin ligases
    Bing Hao
    Structural Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    Mol Cell 26:131-43. 2007
  8. pmc FBW7 mutations in leukemic cells mediate NOTCH pathway activation and resistance to gamma-secretase inhibitors
    Jennifer O'Neil
    Department of Pediatric Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA
    J Exp Med 204:1813-24. 2007
  9. ncbi FBXW7/hCDC4 is a general tumor suppressor in human cancer
    Shahab Akhoondi
    Cancer Center Karolinska, Karolinska Hospital, Stockholm, Sweden
    Cancer Res 67:9006-12. 2007
  10. ncbi Histone demethylation by a family of JmjC domain-containing proteins
    Yu Ichi Tsukada
    Howard Hughes Medical Institute, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599 7295, USA
    Nature 439:811-6. 2006

Detail Information

Publications246 found, 100 shown here

  1. pmc The Fbw7 tumor suppressor regulates glycogen synthase kinase 3 phosphorylation-dependent c-Myc protein degradation
    Markus Welcker
    Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
    Proc Natl Acad Sci U S A 101:9085-90. 2004
    ..Because Fbw7 mediates the degradation of cyclin E, Notch, and c-Jun, as well as c-Myc, the loss of Fbw7 is likely to elicit profound effects on cell proliferation during tumorigenesis...
  2. pmc Systematic analysis and nomenclature of mammalian F-box proteins
    Jianping Jin
    Genes Dev 18:2573-80. 2004
  3. ncbi Phosphorylation-dependent ubiquitination of cyclin E by the SCFFbw7 ubiquitin ligase
    D M Koepp
    Department of Biochemistry and Molecular Biology, Howard Hughes Medical Institute, Baylor College of Medicine, Houston, TX, 77030, USA
    Science 294:173-7. 2001
    ..Multiple F-box proteins contribute to cyclin E stability in yeast, suggesting an overlap in SCF E3 ligase specificity that allows combinatorial control of cyclin E degradation...
  4. pmc The SCFFBW7 ubiquitin ligase complex as a tumor suppressor in T cell leukemia
    Benjamin J Thompson
    Department of Pathology, New York University School of Medicine, New York, NY 10016, USA
    J Exp Med 204:1825-35. 2007
    ..Our data suggest that FBW7 is a novel tumor suppressor in T cell leukemia, and implicate the loss of FBW7 function as a potential mechanism of drug resistance in T-ALL...
  5. ncbi Plant development is regulated by a family of auxin receptor F box proteins
    Nihal Dharmasiri
    Department of Biology, Indiana University, Bloomington, Indiana 47405, USA
    Dev Cell 9:109-19. 2005
    ..Here we show that three additional F box proteins, called AFB1, 2, and 3, also regulate auxin response...
  6. ncbi SKP1 connects cell cycle regulators to the ubiquitin proteolysis machinery through a novel motif, the F-box
    C Bai
    Howard Hughes Medical Institute, Baylor College of Medicine, Houston, Texas 77030, USA
    Cell 86:263-74. 1996
    ..Different skp1 mutants arrest cells in either G1 or G2, suggesting a connection between regulation of proteolysis in different stages of the cycle...
  7. ncbi Structure of a Fbw7-Skp1-cyclin E complex: multisite-phosphorylated substrate recognition by SCF ubiquitin ligases
    Bing Hao
    Structural Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    Mol Cell 26:131-43. 2007
    ....
  8. pmc FBW7 mutations in leukemic cells mediate NOTCH pathway activation and resistance to gamma-secretase inhibitors
    Jennifer O'Neil
    Department of Pediatric Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA
    J Exp Med 204:1813-24. 2007
    ....
  9. ncbi FBXW7/hCDC4 is a general tumor suppressor in human cancer
    Shahab Akhoondi
    Cancer Center Karolinska, Karolinska Hospital, Stockholm, Sweden
    Cancer Res 67:9006-12. 2007
    ..Our study is the first comprehensive screen of FBXW7 mutations in various human malignancies and shows that FBXW7 is a general tumor suppressor in human cancer...
  10. ncbi Histone demethylation by a family of JmjC domain-containing proteins
    Yu Ichi Tsukada
    Howard Hughes Medical Institute, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599 7295, USA
    Nature 439:811-6. 2006
    ..Thus, we identify the JmjC domain as a novel demethylase signature motif and uncover a protein demethylation mechanism that is conserved from yeast to human...
  11. ncbi Multisite phosphorylation by Cdk2 and GSK3 controls cyclin E degradation
    Markus Welcker
    Divisions of Clinical Research and Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
    Mol Cell 12:381-92. 2003
    ..Thus, cyclin E turnover is controlled by multiple biological inputs and cannot be understood in terms of autophosphorylation alone...
  12. ncbi A nucleolar isoform of the Fbw7 ubiquitin ligase regulates c-Myc and cell size
    Markus Welcker
    Divisions of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
    Curr Biol 14:1852-7. 2004
    ..We suggest that interactions between c-Myc and Fbw7gamma within the nucleolus regulate c-Myc's growth-promoting function and that c-Myc activation is likely to be an important oncogenic consequence of Fbw7 loss in cancers...
  13. ncbi FBW7 ubiquitin ligase: a tumour suppressor at the crossroads of cell division, growth and differentiation
    Markus Welcker
    Division of Human Biology, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, Washington 98109, USA
    Nat Rev Cancer 8:83-93. 2008
    ..This Review focuses on structural and functional aspects of FBW7 and its role in the development of cancer...
  14. pmc Phosphorylation-dependent ubiquitination of cyclin D1 by the SCF(FBX4-alphaB crystallin) complex
    Douglas I Lin
    The Leonard and Madlyn Abramson Family Cancer Research Institute and Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Mol Cell 24:355-66. 2006
    ..We conclude that SCF(FBX4-alphaB crystallin) is an E3 ubiquitin ligase that promotes ubiquitin-dependent degradation of Thr286-phosphorylated cyclin D1...
  15. ncbi Inactivation of hCDC4 can cause chromosomal instability
    Harith Rajagopalan
    The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA
    Nature 428:77-81. 2004
    ..Our data suggest that chromosomal instability is caused by specific genetic alterations in a large fraction of human cancers and can occur before malignant conversion...
  16. ncbi EIN3-dependent regulation of plant ethylene hormone signaling by two arabidopsis F box proteins: EBF1 and EBF2
    Thomas Potuschak
    Institut de Biologie Moleculaire des Plantes du CNRS, 12 rue du Général Zimmer, 67084 Cedex, Strasbourg, France
    Cell 115:679-89. 2003
    ..Here, we identify two Arabidopsis F box proteins called EBF1 and EBF2 that interact physically with EIN3/EIL transcription factors...
  17. pmc WD40 repeat propellers define a ubiquitin-binding domain that regulates turnover of F box proteins
    Natasha Pashkova
    Department of Molecular Physiology and Biophysics, University of Iowa, Iowa City, IA 52242, USA
    Mol Cell 40:433-43. 2010
    ..Collectively, our results reveal a molecular mechanism that may account for how ubiquitin controls a broad spectrum of cellular activities...
  18. pmc Phosphorylation-dependent degradation of c-Myc is mediated by the F-box protein Fbw7
    Masayoshi Yada
    Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, Maidashi, Higashi ku, Fukuoka, Fukuoka, Japan
    EMBO J 23:2116-25. 2004
    ..Accumulation of c-Myc was also apparent in mouse Fbw7-/- embryonic stem cells. These observations suggest that two F-box proteins, Fbw7 and Skp2, differentially regulate c-Myc stability by targeting MB1 and MB2, respectively...
  19. ncbi The ubiquitin ligase SCFFbw7 antagonizes apoptotic JNK signaling
    Abdolrahman S Nateri
    Mammalian Genetics Laboratory, Cancer Research UK, London Research Institute, Lincoln s Inn Fields Laboratories, 44 Lincoln s Inn Fields, London WC2A 3PX, UK
    Science 303:1374-8. 2004
    ..SCF(Fbw7) therefore antagonizes the apoptotic c-Jun-dependent effector arm of JNK signaling, allowing neurons to tolerate potentially neurotoxic JNK activity...
  20. ncbi CDC4 mutations occur in a subset of colorectal cancers but are not predicted to cause loss of function and are not associated with chromosomal instability
    Zoe Kemp
    Molecular and Population Genetics Laboratory, London Research Institute, Cancer Research UK
    Cancer Res 65:11361-6. 2005
    ..CDC4 mutations may be selected primarily to drive progression through the cell cycle although CIN might be an important secondary effect in some cancers...
  21. ncbi Suprafacial orientation of the SCFCdc4 dimer accommodates multiple geometries for substrate ubiquitination
    Xiaojing Tang
    Centre for Systems Biology, Samuel Lunenfeld Research Institute, Toronto, Ontario, Canada M5G 1X5
    Cell 129:1165-76. 2007
    SCF ubiquitin ligases recruit substrates for degradation via F box protein adaptor subunits. WD40 repeat F box proteins, such as Cdc4 and beta-TrCP, contain a conserved dimerization motif called the D domain...
  22. ncbi Mechanism of auxin perception by the TIR1 ubiquitin ligase
    Xu Tan
    Department of Pharmacology, University of Washington, School of Medicine, Box 357280, Seattle, Washington 98195, USA
    Nature 446:640-5. 2007
    ..By filling in a hydrophobic cavity at the protein interface, auxin enhances the TIR1-substrate interactions by acting as a 'molecular glue'. Our results establish the first structural model of a plant hormone receptor...
  23. pmc Defective cardiovascular development and elevated cyclin E and Notch proteins in mice lacking the Fbw7 F-box protein
    Michael T Tetzlaff
    Department of Human and Molecular Genetics, Texas Children s Hospital, Houston, TX 77030, USA
    Proc Natl Acad Sci U S A 101:3338-45. 2004
    ..These data suggest essential functions for Fbw7 in controlling cyclin E and Notch signaling pathways in the mouse...
  24. ncbi FBXO31 is the chromosome 16q24.3 senescence gene, a candidate breast tumor suppressor, and a component of an SCF complex
    Raman Kumar
    Breast Cancer Genetics Group, Dame Roma Mitchell Cancer Research Laboratories, Department of Medicine, University of Adelaide and Hanson Institute, Institute of Medical and Veterinary Science Adelaide, Australia
    Cancer Res 65:11304-13. 2005
    ..We propose that FBXO31 functions as a tumor suppressor by generating SCF(FBXO31) complexes that target particular substrates, critical for the normal execution of the cell cycle, for ubiquitination and subsequent degradation...
  25. ncbi Fbw7 promotes ubiquitin-dependent degradation of c-Myb: involvement of GSK3-mediated phosphorylation of Thr-572 in mouse c-Myb
    K Kitagawa
    Department of Biochemistry 1, Hamamatsu University School of Medicine, Higashi ku, Hamamatsu, Shizuoka, Japan
    Oncogene 28:2393-405. 2009
    ..In consequence, the c-Myb protein was markedly stabilized by the substitution of Thr-572 to Ala. These observations suggest that SCF(Fbw7) ubiquitin ligase regulates phosphorylation-dependent degradation of c-Myb protein...
  26. ncbi F-box proteins are receptors that recruit phosphorylated substrates to the SCF ubiquitin-ligase complex
    D Skowyra
    Verna and Marrs McLean Department of Biochemistry, Baylor College of Medicine, Houston, Texas 77030, USA
    Cell 91:209-19. 1997
    ..SCF complexes couple protein kinase signaling pathways to the control of protein abundance...
  27. ncbi Fbw7 and Usp28 regulate myc protein stability in response to DNA damage
    Nikita Popov
    Institute of Molecular Biology and Tumor Research, Emil Mannkopff Str 2, Marburg, Germany
    Cell Cycle 6:2327-31. 2007
    ..Our data extend previous observations that link Myc function to the cellular response to DNA damage...
  28. pmc Mammalian Emi2 mediates cytostatic arrest and transduces the signal for meiotic exit via Cdc20
    Shisako Shoji
    Laboratory of Mammalian Molecular Embryology, RIKEN Center for Developmental Biology, Chuo Ku, Kobe, Japan
    EMBO J 25:834-45. 2006
    ..These studies show in intact oocytes that the interaction of Emi2 with Cdc20 links activating stimuli to meiotic resumption at fertilization and during parthenogenesis in mammals...
  29. pmc Control of hematopoietic stem cell quiescence by the E3 ubiquitin ligase Fbw7
    Benjamin J Thompson
    Department of Pathology, New York University School of Medicine, New York, NY 10016, USA
    J Exp Med 205:1395-408. 2008
    ....
  30. ncbi The small-molecule inhibitor BI 2536 reveals novel insights into mitotic roles of polo-like kinase 1
    Peter Lenart
    Research Institute of Molecular Pathology, A 1030 Vienna, Austria
    Curr Biol 17:304-15. 2007
    ..Cdk1 and Aurora kinase studies have been facilitated by small-molecule inhibitors, but few if any potent Plk1 inhibitors have been identified...
  31. ncbi Identification of the pollen determinant of S-RNase-mediated self-incompatibility
    Paja Sijacic
    Integrative Biosciences Graduate Degree Program, The Pennsylvania State University, 403 Althouse Laboratory, University Park, Pennsylvania 16802, USA
    Nature 429:302-5. 2004
    ..We conclude that PiSLF encodes the pollen self-incompatibility determinant...
  32. pmc Mouse Emi2 is required to enter meiosis II by reestablishing cyclin B1 during interkinesis
    Suzanne Madgwick
    Institute for Cell and Molecular Biosciences, The Medical School, University of Newcastle, Newcastle NE2 4HH, England, UK
    J Cell Biol 174:791-801. 2006
    ....
  33. pmc Ubiquitin-dependent degradation of multiple F-box proteins by an autocatalytic mechanism
    J M Galan
    Swiss Institute for Experimental Cancer Research, Chemin des Boveresses 155, 1066 Epalinges VD, Switzerland
    Proc Natl Acad Sci U S A 96:9124-9. 1999
    ....
  34. pmc Fbxw7 acts as a critical fail-safe against premature loss of hematopoietic stem cells and development of T-ALL
    Sahoko Matsuoka
    Department of Cell Differentiation, The Sakaguchi Laboratory, School of Medicine, Keio University, Tokyo 160 8582, Japan
    Genes Dev 22:986-91. 2008
    ..Thus, Fbxw7 functions as a fail-safe mechanism against both premature HSC loss and leukemogenesis...
  35. pmc A role for the anaphase-promoting complex inhibitor Emi2/XErp1, a homolog of early mitotic inhibitor 1, in cytostatic factor arrest of Xenopus eggs
    Jeffrey J Tung
    Department of Pathology, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA 94305, USA
    Proc Natl Acad Sci U S A 102:4318-23. 2005
    ..These results identify Emi2 as a candidate CSF maintenance protein...
  36. ncbi Ubiquitylation of cyclin E requires the sequential function of SCF complexes containing distinct hCdc4 isoforms
    Frank van Drogen
    Department of Molecular Biology, The Scripps Research Institute, La Jolla, California 92037, USA
    Mol Cell 23:37-48. 2006
    ..Furthermore, in the context of Cdc4alpha and cyclin E, mutational data suggest that Pin1 isomerizes a noncanonical proline-proline bond, with the possibility that Cdc4alpha may serve as a cofactor for altering the specificity of Pin1...
  37. ncbi The SCF ubiquitin ligase: insights into a molecular machine
    Timothy Cardozo
    Department of Pathology and New York University Cancer Institute, New York University Medical Center, 550 First Avenue, MSB 599, New York, New York 10016, USA
    Nat Rev Mol Cell Biol 5:739-51. 2004
    ..Here we explore a unifying and structurally detailed view of SCF-mediated proteolytic control of cellular processes that has been revealed by recent studies...
  38. ncbi hCDC4 gene mutations in endometrial cancer
    Charles H Spruck
    Department of Molecular Biology, The Scripps Research Institute, La Jolla, California 92037, USA
    Cancer Res 62:4535-9. 2002
    ..Our results show that the hCDC4 gene is mutated in primary human tumors and suggest that it may function as a tumor suppressor in the genesis of many human cancers...
  39. ncbi The tumor suppressor gene hCDC4 is frequently mutated in human T-cell acute lymphoblastic leukemia with functional consequences for Notch signaling
    Alena Malyukova
    Department of Oncology Pathology, Cancer Center Karolinska, Karolinska sjukhuset, Sweden
    Cancer Res 67:5611-6. 2007
    ....
  40. ncbi A complex of Cdc4p, Skp1p, and Cdc53p/cullin catalyzes ubiquitination of the phosphorylated CDK inhibitor Sic1p
    R M Feldman
    Division of Biology, California Institute of Technology, Pasadena 91125, USA
    Cell 91:221-30. 1997
    ..Taken together, these data illuminate the molecular basis for the G1/S transition in budding yeast and suggest a general mechanism for phosphorylation-targeted ubiquitination in eukaryotes...
  41. ncbi Multisite phosphorylation of a CDK inhibitor sets a threshold for the onset of DNA replication
    P Nash
    Programme in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto M5G 1X5, Canada
    Nature 414:514-21. 2001
    ..Multisite phosphorylation may be a more general mechanism to set thresholds in regulated protein-protein interactions...
  42. pmc SCF ubiquitin protein ligases and phosphorylation-dependent proteolysis
    A R Willems
    Programme in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Canada
    Philos Trans R Soc Lond B Biol Sci 354:1533-50. 1999
    ..As many F-box proteins can be found in sequence databases, it appears that a host of cellular pathways will be regulated by SCF-dependent proteolysis...
  43. ncbi Fbxw7/Cdc4 is a p53-dependent, haploinsufficient tumour suppressor gene
    Jian Hua Mao
    Cancer Research Institute, University of California at San Francisco, 2340 Sutter Street, San Francisco, California 94143, USA
    Nature 432:775-9. 2004
    ..We propose that p53-dependent loss of Fbxw7 leads to genetic instability by mechanisms that might involve the activation of Aurora-A, providing a rationale for the early occurrence of these mutations in human cancers...
  44. pmc Regulation of NF-kappaB by NSD1/FBXL11-dependent reversible lysine methylation of p65
    Tao Lu
    Department of Molecular Genetics, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA
    Proc Natl Acad Sci U S A 107:46-51. 2010
    ..We conclude that reversible lysine methylation of NF-kappaB is an important element in the complex regulation of this key transcription factor...
  45. ncbi A direct link of the Mos-MAPK pathway to Erp1/Emi2 in meiotic arrest of Xenopus laevis eggs
    Daigo Inoue
    Department of Biology, Graduate School of Sciences, Kyushu University, Hakozaki 6 10 1, Fukuoka 812 8581, Japan
    Nature 446:1100-4. 2007
    ..These results clarify the direct link of the classical Mos-MAPK pathway to Erp1 in meiotic arrest of vertebrate oocytes...
  46. ncbi The F box protein Dsg1/Mdm30 is a transcriptional coactivator that stimulates Gal4 turnover and cotranscriptional mRNA processing
    Masafumi Muratani
    Watson School of Biological Sciences, 1 Bungtown Road, Cold Spring Harbor, New York 11724, USA
    Cell 120:887-99. 2005
    ..We propose that Gal4 ubiquitylation and destruction are required for initiation-competent transcription complexes to transition to fully mature elongating complexes capable of appropriate mRNA processing...
  47. ncbi Mouse Fbw7/Sel-10/Cdc4 is required for notch degradation during vascular development
    Ryosuke Tsunematsu
    Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan
    J Biol Chem 279:9417-23. 2004
    ..Expression of Notch1, -2, or -3 or of cyclin E was unaffected in Fbw7(-/-) embryos. Mammalian Fbw7 thus appears to play an indispensable role in negative regulation of the Notch4-Hey1 pathway and is required for vascular development...
  48. ncbi Mechanisms of tumor suppression by the SCF(Fbw7)
    Alex C Minella
    Division of Clinical Research and Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washinton 98109 1024, USA
    Cell Cycle 4:1356-9. 2005
    ..In this review we discuss the activities of the SCF(Fbw7) in the context of its role as a tumor suppressor and highlight recent findings demonstrating that dominant oncogenes disable Fbw7 function...
  49. ncbi Human F-box protein hCdc4 targets cyclin E for proteolysis and is mutated in a breast cancer cell line
    H Strohmaier
    Department of Molecular Biology, MB 7, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
    Nature 413:316-22. 2001
    ..The gene encoding hCdc4 was found to be mutated in a cell line derived from breast cancer that expressed extremely high levels of cyclin E...
  50. ncbi The ubiquitin-specific protease USP28 is required for MYC stability
    Nikita Popov
    Institute of Molecular Biology and Tumor Research, Emil Mannkopff Str 2, 35033 Marburg, Germany
    Nat Cell Biol 9:765-74. 2007
    ..High expression levels of USP28 are found in colon and breast carcinomas, and stabilization of MYC by USP28 is essential for tumour-cell proliferation...
  51. ncbi The Arabidopsis F-box protein TIR1 is an auxin receptor
    Stefan Kepinski
    Department of Biology, University of York, Box 373, York YO10 5YW, UK
    Nature 435:446-51. 2005
    ..Here we show that this modification involves the direct binding of auxin to TIR1 and thus that TIR1 is an auxin receptor mediating transcriptional responses to auxin...
  52. pmc Expression of 10 S-class SLF-like genes in Nicotiana alata pollen and its implications for understanding the pollen factor of the S locus
    David Wheeler
    Plant Cell Biology Research Centre, School of Botany, University of Melbourne, Parkville, Victoria 3010, Australia
    Genetics 177:2171-80. 2007
    ..Finally, the different topologies of the phylogenetic trees produced using available SLF-related sequences and those produced using S-RNase sequences suggests that pollen S and the S-RNase have different evolutionary histories...
  53. pmc Plk1 regulates activation of the anaphase promoting complex by phosphorylating and triggering SCFbetaTrCP-dependent destruction of the APC Inhibitor Emi1
    David V Hansen
    Department of Pathology, Stanford University School of Medicine, Palo Alto, CA 94305, USA
    Mol Biol Cell 15:5623-34. 2004
    ..These data support the hypothesis that Plk1 activates the APC by directing the SCF-dependent destruction of Emi1 in prophase...
  54. pmc Met30p, a yeast transcriptional inhibitor that responds to S-adenosylmethionine, is an essential protein with WD40 repeats
    D Thomas
    Centre de Genetique Moleculaire, Centre National de la Recherche Scientifique, Gif sur Yvette, France
    Mol Cell Biol 15:6526-34. 1995
    ..By the two-hybrid method, we showed that Met30p interacts with Met4p and identified a region of Met4p involved in this interaction. Further analysis reveals that expression of Met30p is essential for cell viability...
  55. ncbi Ubiquitination of cyclin-dependent kinase inhibitor, Xic1, is mediated by the Xenopus F-box protein xSkp2
    Horng Ru Lin
    Department of Molecular Medicine, Institute of Biotechnology, University of Texas Health Science Center, San Antonio, Texas 78245 3207, USA
    Cell Cycle 5:304-14. 2006
    ..These studies provide the first characterization of the SCF in Xenopus and its role in the ubiquitination of CDK inhibitor, Xic1, during DNA replication initiation...
  56. ncbi Regulating the yeast kinetochore by ubiquitin-dependent degradation and Skp1p-mediated phosphorylation
    K B Kaplan
    Department of Biology, Massachusetts Institute of Technology, Cambridge 02139, USA
    Cell 91:491-500. 1997
    ..We propose that coupled activation and destruction link the assembly of Cbf3p to the duplication of centromeres in S phase...
  57. pmc Degradation of Hof1 by SCF(Grr1) is important for actomyosin contraction during cytokinesis in yeast
    Marc Blondel
    CNRS, Station Biologique, UMR7150, Amyloids and Cell Division Cycle Laboratory, Place G Teissier, Roscoff, Bretagne, France
    EMBO J 24:1440-52. 2005
    ..SCF(Grr1)-mediated degradation of Hof1 may thus represent a novel mechanism to couple exit from mitosis with initiation of cytokinesis...
  58. ncbi The SV40 large T antigen contains a decoy phosphodegron that mediates its interactions with Fbw7/hCdc4
    Markus Welcker
    Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA
    J Biol Chem 280:7654-8. 2005
    ..Our data suggest that LT competes with cellular proteins for Fbw7 binding in a substrate-like fashion...
  59. pmc Xenopus polo-like kinase Plx1 regulates XErp1, a novel inhibitor of APC/C activity
    Andreas Schmidt
    Chemical Biology, Independent Research Group, Max Planck Institute of Biochemistry, 82152 Martinsried, Germany
    Genes Dev 19:502-13. 2005
    ..Plx1 phosphorylates XErp1 in vitro at a site that targets XErp1 for degradation upon CSF release. Thus, our data lead to a model of APC/C activation in Xenopus egg extract in which Plx1 targets the APC/C inhibitor XErp1 for degradation...
  60. pmc Mutations in Fbx4 inhibit dimerization of the SCF(Fbx4) ligase and contribute to cyclin D1 overexpression in human cancer
    Olena Barbash
    Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Cancer Cell 14:68-78. 2008
    ..Collectively, these data reveal that inactivation of the cyclin D1 E3 ligase likely contributes to cyclin D1 overexpression in a significant fraction of human cancer...
  61. ncbi Competitive interaction between two functional S-haplotypes confer self-compatibility on tetraploid Chinese cherry (Prunus pseudocerasus Lindl. CV. Nanjing Chuisi)
    S X Huang
    College of Horticulture, Nanjing Agricultural University, Nanjing 210095, China
    Plant Cell Rep 27:1075-85. 2008
    ..Furthermore, in terms of recognition specificity, diploid pollen grains carrying PpsS-3'-haplotype are equal to monoploid pollen grains carrying the other functional S-haplotype...
  62. ncbi NEDD8 modification of CUL1 dissociates p120(CAND1), an inhibitor of CUL1-SKP1 binding and SCF ligases
    Jidong Liu
    Department of Biochemistry and Biophysics, Lineberger Comprehensive Cancer Center, Program in Molecular Biology and Biotechnology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
    Mol Cell 10:1511-8. 2002
    ..We suggest that by restricting SKP1-CUL1 interaction, CAND1 regulated the assembly of productive SCF ubiquitin ligases, allowing a common CUL1-ROC core to be utilized by a large number of SKP1-F box-substrate subcomplexes...
  63. pmc The APC/C inhibitor, Emi1, is essential for prevention of rereplication
    Yuichi J Machida
    Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA
    Genes Dev 21:184-94. 2007
    ..These data suggest that Emi1 plays a critical role in preserving genome integrity by blocking rereplication, revealing a previously unrecognized function of this inhibitor of APC/C...
  64. ncbi The C. elegans F-box/WD-repeat protein LIN-23 functions to limit cell division during development
    E T Kipreos
    Department of Cellular Biology, The University of Georgia, Athens, Georgia 30602, USA
    Development 127:5071-82. 2000
    ..In contrast, lin-23 functions cell autonomously to negatively regulate cell cycle progression, thereby allowing cell cycle exit in response to developmental signals...
  65. ncbi The after-hours mutant reveals a role for Fbxl3 in determining mammalian circadian period
    Sofia I H Godinho
    Medical Research Council MRC Mammalian Genetics Unit, Harwell, Oxfordshire OX11 0RD, UK
    Science 316:897-900. 2007
    ..The Afh allele significantly affected Per2 expression and delayed the rate of Cry protein degradation in Per2::Luciferase tissue slices. Our in vivo and in vitro studies reveal a central role for Fbxl3 in mammalian circadian timekeeping...
  66. ncbi Prophase destruction of Emi1 by the SCF(betaTrCP/Slimb) ubiquitin ligase activates the anaphase promoting complex to allow progression beyond prometaphase
    Florence Margottin-Goguet
    Department of Pathology, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA 94305, USA
    Dev Cell 4:813-26. 2003
    ..We hypothesize that Emi1 destruction relieves a late prophase checkpoint for APC activation...
  67. ncbi JHDM1B/FBXL10 is a nucleolar protein that represses transcription of ribosomal RNA genes
    David Frescas
    Department of Pathology, NYU Cancer Institute, New York University School of Medicine, 550 First Avenue, New York, New York 10016, USA
    Nature 450:309-13. 2007
    ....
  68. pmc Emi1 stably binds and inhibits the anaphase-promoting complex/cyclosome as a pseudosubstrate inhibitor
    Julie J Miller
    Program in Molecular Pharmacology, Stanford University School of Medicine, Stanford, California 94305, USA
    Genes Dev 20:2410-20. 2006
    ..The combination of a degron/E3 recognition site and an anti-ligase function in Emi1 suggests a general model for how E3 substrates evolve to become pseudosubstrate inhibitors...
  69. pmc Ras activity regulates cyclin E degradation by the Fbw7 pathway
    Alex C Minella
    Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
    Proc Natl Acad Sci U S A 102:9649-54. 2005
    ..Thus, we conclude that Ras activity regulates Fbw7-mediated cyclin E proteolysis and suggest that impaired cyclin E proteolysis is a mechanism through which Ras mutations promote tumorigenesis...
  70. pmc Circadian mutant Overtime reveals F-box protein FBXL3 regulation of cryptochrome and period gene expression
    Sandra M Siepka
    Howard Hughes Medical Institute, Northwestern University, 2205 Tech Drive, Evanston, IL 60208, USA
    Cell 129:1011-23. 2007
    ..Thus, Fbxl3(Ovtm) defines a molecular link between CRY turnover and CLOCK/BMAL1-dependent circadian transcription to modulate circadian period...
  71. ncbi Slug stability is dynamically regulated during neural crest development by the F-box protein Ppa
    Ann E Vernon
    Department of Biochemistry, Molecular Biology and Cell Biology, Northwestern University, Evanston, IL 60208, USA
    Development 133:3359-70. 2006
    ..These results provide novel insight into the regulation of Slug, a protein that plays a central role in neural crest precursor formation, as well as in developmental and pathological epithelial to mesenchymal transitions...
  72. ncbi The amino-terminal TPR domain of Dia2 tethers SCF(Dia2) to the replisome progression complex
    Hiroko Morohashi
    Cancer Research UK Paterson Institute for Cancer Research, University of Manchester, UK
    Curr Biol 19:1943-9. 2009
    ..Our findings suggest that the amino-terminal domains of other F box proteins might also play an analogous regulatory role, controlling the localization of the cognate SCF complexes.
  73. ncbi Phosphorylation of Erp1 by p90rsk is required for cytostatic factor arrest in Xenopus laevis eggs
    Tomoko Nishiyama
    Laboratory of Cell and Developmental Biology, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259 Nagatsuta, Midori ku, Yokohama 226 8501, Japan
    Nature 446:1096-9. 2007
    ..Thus, Mos and Erp1 collaboratively establish and maintain metaphase II arrest in Xenopus eggs. The link between Mos and Erp1 provides a molecular explanation for the integral mechanism of CSF arrest in unfertilized vertebrate eggs...
  74. pmc Role of the Schizosaccharomyces pombe F-Box DNA helicase in processing recombination intermediates
    Takashi Morishita
    Department of Molecular Microbiology, Research Institute for Microbial Diseases, Osaka University, 3 1 Yamada oka, Suita, Osaka 565 0871, Japan
    Mol Cell Biol 25:8074-83. 2005
    ..Focus formation of Fbh1 protein was induced by treatment that damages DNA. Thus, the F-box DNA helicase appears to process toxic recombination intermediates, the formation of which is dependent on the function of Rhp51...
  75. pmc Activation of the S-phase checkpoint inhibits degradation of the F-box protein Dia2
    Andrew C Kile
    Department of Genetics, Cell Biology and Development, 6 160 Jackson Hall, 321 Church St, S E, Minneapolis, MN 55455, USA
    Mol Cell Biol 30:160-71. 2010
    ..Together, our results suggest that Dia2 protein turnover does not involve an autocatalytic mechanism and that Dia2 proteolysis is inhibited by activation of the replication stress response...
  76. ncbi F-box proteins everywhere
    Esther Lechner
    Institut de Biologie Moleculaire des Plantes du CNRS, 12 rue du Général Zimmer, 67084 Strasbourg Cedex, France
    Curr Opin Plant Biol 9:631-8. 2006
    ..Interestingly, viruses and even pathogenic bacteria have also found ways to hijack the plant SCF and to reprogram it for their own purposes...
  77. pmc Conditional inactivation of Fbxw7 impairs cell-cycle exit during T cell differentiation and results in lymphomatogenesis
    Ichiro Onoyama
    Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, Higashi ku, Fukuoka 812 8582, Japan
    J Exp Med 204:2875-88. 2007
    ....
  78. pmc The F-Box DNA helicase Fbh1 prevents Rhp51-dependent recombination without mediator proteins
    Fekret Osman
    Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, United Kingdom
    Mol Cell Biol 25:8084-96. 2005
    ..Furthermore, analysis of different fbh1 mutant alleles suggests that both the F-box and helicase activities of Fbh1 contribute to controlling Rhp51...
  79. pmc Inducible dissociation of SCF(Met30) ubiquitin ligase mediates a rapid transcriptional response to cadmium
    Regine Barbey
    Centre de Genetique Moleculaire, Centre National de la Recherche Scientifique, Gif sur Yvettte, France
    EMBO J 24:521-32. 2005
    ..Post-translational control of SCF(Met30) assembly by a physiological stress to allow rapid induction of a protective gene expression program represents a novel mode of regulation in the ubiquitin system...
  80. ncbi SCFFbxl3 controls the oscillation of the circadian clock by directing the degradation of cryptochrome proteins
    Luca Busino
    Department of Pathology, NYU Cancer Institute, New York University School of Medicine, 550 First Avenue, MSB 599, New York, NY 10016, USA
    Science 316:900-4. 2007
    ..Silencing of Fbxl3 produced no effect in Cry1-/-;Cry2-/- cells, which shows that Fbxl3 controls clock oscillations by mediating the degradation of CRY proteins...
  81. ncbi An SCF-like ubiquitin ligase complex that controls presynaptic differentiation
    Edward H Liao
    Department of Medical Genetics and Microbiology, Samuel Lunenfeld Research Institute, University of Toronto, Ontario, Canada M5G 1X5
    Nature 430:345-50. 2004
    ..This neuron-specific, SCF-like complex therefore provides a localized signal to attenuate presynaptic differentiation...
  82. pmc SIC1 is ubiquitinated in vitro by a pathway that requires CDC4, CDC34, and cyclin/CDK activities
    R Verma
    Division of Biology, California Institute of Technology, Pasadena 91125, USA
    Mol Biol Cell 8:1427-37. 1997
    ..The complementary C-terminal segment of SIC1 binds to the S-phase cyclin CLB5, indicating a modular structure for SIC1...
  83. ncbi Fus3-regulated Tec1 degradation through SCFCdc4 determines MAPK signaling specificity during mating in yeast
    Song Chou
    Department of Biological Chemistry, University of California, Irvine, Irvine, CA 92697, USA
    Cell 119:981-90. 2004
    ..Tec1T273V blocks Tec1 ubiquitination and degradation and allows the induction of filamentation genes in response to pheromone. Thus, Fus3 inhibits filamentous growth during mating by degrading Tec1...
  84. ncbi Regulation of the cell cycle by SCF-type ubiquitin ligases
    Keiichi I Nakayama
    Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, 3 1 1 Maidashi, Higashi ku, Fukuoka, Fukuoka 812 8582, Japan
    Semin Cell Dev Biol 16:323-33. 2005
    ..Clinical evidence also suggests that dysregulation of these F-box proteins contributes to human cancers...
  85. ncbi The F-box protein TIR1 is an auxin receptor
    Nihal Dharmasiri
    Department of Biology, Indiana University, Bloomington, Indiana 47405, USA
    Nature 435:441-5. 2005
    ..Finally, TIR1 synthesized in insect cells binds Aux/IAA proteins in an auxin-dependent manner. Together, these results indicate that TIR1 is an auxin receptor that mediates Aux/IAA degradation and auxin-regulated transcription...
  86. ncbi The evi5 oncogene regulates cyclin accumulation by stabilizing the anaphase-promoting complex inhibitor emi1
    Adam G Eldridge
    Department of Cancer Biology, Stanford University School of Medicine, CA 94305, USA
    Cell 124:367-80. 2006
    ..We propose that the balance of Evi5 and Polo-like kinase activities determines the timely accumulation of Emi1 and cyclin, ensuring mitotic fidelity...
  87. ncbi Calcium elevation at fertilization coordinates phosphorylation of XErp1/Emi2 by Plx1 and CaMK II to release metaphase arrest by cytostatic factor
    Junjun Liu
    Howard Hughes Medical Institute and Department of Pharmacology, University of Colorado School of Medicine, Denver, Colorado 80262, USA
    Curr Biol 15:1458-68. 2005
    ..However, connections between the Plx1 pathway and the CaMKII pathway have not been identified...
  88. ncbi Fission yeast Mcl1 interacts with SCF(Pof3) and is required for centromere formation
    Yasmine M Mamnun
    Laboratory of Cell Regulation, London Research Institute, Cancer Research UK, 44 Lincoln s Inn Fields, London WC2A 3PX, UK
    Biochem Biophys Res Commun 350:125-30. 2006
    ..Importantly, we identity a novel, specific role for Mcl1 in the transcriptional silencing and the localisation of CENP-A at the centromeres...
  89. pmc sel-10, a negative regulator of lin-12 activity in Caenorhabditis elegans, encodes a member of the CDC4 family of proteins
    E J Hubbard
    Department of Biochemistry and Molecular Biophysics, Howard Hughes Medical Institute, New York, New York 10032, USA
    Genes Dev 11:3182-93. 1997
    ..We propose that SEL-10 promotes the ubiquitin-mediated turnover of LIN-12/Notch proteins, and discuss potential roles for the regulation of lin-12/Notch activity by sel-10 in cell fate decisions and tumorigenesis...
  90. pmc CaMKII and polo-like kinase 1 sequentially phosphorylate the cytostatic factor Emi2/XErp1 to trigger its destruction and meiotic exit
    David V Hansen
    Program in Cancer Biology, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA 94305, USA
    Proc Natl Acad Sci U S A 103:608-13. 2006
    ....
  91. ncbi Overexpression of the anaphase promoting complex/cyclosome inhibitor Emi1 leads to tetraploidy and genomic instability of p53-deficient cells
    Norman L Lehman
    Department of Pathology, Stanford University, Stanford, California 94305, USA
    Cell Cycle 5:1569-73. 2006
    ..This represents a potentially important mechanism by which pRb and p53 dysfunction may contribute to tumorigenesis through the generation of genomic instability...
  92. ncbi The v-Jun point mutation allows c-Jun to escape GSK3-dependent recognition and destruction by the Fbw7 ubiquitin ligase
    Wenyi Wei
    Department of Medical Oncology, Dana Farber Cancer Institute and Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Cancer Cell 8:25-33. 2005
    ..These findings explain the enhanced stability and oncogenicity of v-Jun relative to its cellular counterpart and reveal that GSK3 and Fbw7 coordinately regulate c-Jun and c-Myc...
  93. pmc Role of Polo-like kinase in the degradation of early mitotic inhibitor 1, a regulator of the anaphase promoting complex/cyclosome
    Yakir Moshe
    Unit of Biochemistry, The Bruce Rappaport Faculty of Medicine, Technion Israel Institute of Technology, Haifa 31096, Israel
    Proc Natl Acad Sci U S A 101:7937-42. 2004
    ..Transfection with an small interfering RNA duplex directed against Plk1 caused the accumulation of Emi1 in mitotically arrested HeLa cells. It is suggested that phosphorylation of Emi1 by Plk1 is involved in its degradation in mitosis...
  94. ncbi Multisite phosphorylation and the countdown to S phase
    R J Deshaies
    Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA
    Cell 107:819-22. 2001
    ..This numerical wizardry suggests how analog inputs can be rectified to digital outputs. Unraveling the counting mechanism promises to generate new insights into the architecture of protein nanoprocessors...
  95. ncbi Regulation of the G1 to S transition by the ubiquitin pathway
    L M DeSalle
    Department of Pathology and Kaplan Comprehensive Cancer Center, MSB 548, New York University Medical Center, 550 First Avenue, New York, NY 10016, USA
    FEBS Lett 490:179-89. 2001
    ..Thus, understanding the mechanisms that confer specificity to the ubiquitin system will allow the development of novel therapeutic approaches to target aberrations in this pathway underlying tumorigenesis and other human pathologies...
  96. ncbi Archipelago regulates Cyclin E levels in Drosophila and is mutated in human cancer cell lines
    K H Moberg
    Massachusetts General Hospital Cancer Center, Charlestown, MA 02129, USA
    Nature 413:311-6. 2001
    ..These findings implicate archipelago in developmentally regulated degradation of Cyclin E and potentially in the pathogenesis of human cancers...
  97. ncbi E2F-dependent accumulation of hEmi1 regulates S phase entry by inhibiting APC(Cdh1)
    Jerry Y Hsu
    Department of Pathology and Program in Biophysics, Stanford University School of Medicine, CA 94305, USA
    Nat Cell Biol 4:358-66. 2002
    ..These data suggest that E2F can activate both transcription of cyclin A and the hEmi1-dependent stabilization of APC(Cdh1) targets, such as cyclin A, to promote S phase entry...
  98. pmc Skp1p and the F-box protein Rcy1p form a non-SCF complex involved in recycling of the SNARE Snc1p in yeast
    J M Galan
    Swiss Institute for Experimental Cancer Research, 1066 Epalinges VD, Switzerland
    Mol Cell Biol 21:3105-17. 2001
    ..Importantly, Skp1p was the only major partner that copurified with Rcy1p. Our results thus suggest that a complex composed of Rcy1p and Skp1p but not other SCF components may play a direct role in recycling of internalized proteins...
  99. ncbi An essential domain within Cdc34p is required for binding to a complex containing Cdc4p and Cdc53p in Saccharomyces cerevisiae
    N Mathias
    Department of Biochemistry and Molecular Biology, Indiana University School of Medicine and the Walther Oncology Center, Indianapolis, Indiana, 46202 5122, USA
    J Biol Chem 273:4040-5. 1998
    ..This suggests that all Cdc34p substrates are ubiquitinated by a similar high molecular weight complex...
  100. ncbi Fbxw7 contributes to tumor suppression by targeting multiple proteins for ubiquitin-dependent degradation
    Yo Fujii
    Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, 3 1 1 Maidashi, Higashi ku, Fukuoka 812 8582
    Cancer Sci 97:729-36. 2006
    ..Fbxw7 seems to regulate the levels of multiple targets to suppress cancer development...
  101. ncbi Grr1 functions in the ubiquitin pathway in Saccharomyces cerevisiae through association with Skp1
    T Kishi
    Department of Molecular Genetics, National Institute of Genetics, Shizuoka ken, Japan
    Mol Gen Genet 257:143-8. 1998
    ..Furthermore, Grr1 bound Skp1 directly in vitro. These results strongly suggest that Grr1 functions in the ubiquitin pathway through association with Skp1...

Research Grants62

  1. A NOVEL F BOX PROTEIN REGULATING MITOSIS
    Peter Jackson; Fiscal Year: 2004
    ..Understanding how SBP5 blocks mitosis and induces apoptosis may provide important insight for creating new cancer chemotherapeutic drugs that act similarly or synergistically with vinca alkaloids and Taxol. ..
  2. Mechanistic validation of SCF E3 ligase as a cancer and radiosensitizing target
    Yi Sun; Fiscal Year: 2013
    ..This study will validate SCF E3 ubiquitin ligase as an anticancer and radiosensitizing target and MLN4924, a newly discovered SCF E3 ligase inhibitor, as a tumor-selective and radiosensitizing agent for cancer therapy. ..
  3. Orientia tsutsugamushi modulation of host cell ubiquitination machinery
    Jason A Carlyon; Fiscal Year: 2013
    ..In Aim 2, we will close an important knowledge gap by identifying the Anks that the pathogen expresses as it establishes infection in each of the 3 biologically relevant host cells. ..
  4. Role of SAG/RBX2 E3 Ubiquitin Ligase in Skin Carcinogenesis
    Yi Sun; Fiscal Year: 2013
    ....
  5. Mechanisms of tumor suppression by Fbw7
    Jonathan E Grim; Fiscal Year: 2010
    ..As such, it is a crucial step towards developing treatment strategies for tumors associated with this pathway. ..
  6. SAG E3 ubiquitin ligase in regulation of transformation and carcinogenesis
    Yi Sun; Fiscal Year: 2013
    ....
  7. Role of the SCF/FBX011 ubiquitin ligase in the control of cell proliferation
    Michele Pagano; Fiscal Year: 2013
    ..Rossi. ..
  8. Role of the SCF/Fbxo15 ubiquitin ligase in stem cells and cancer biology
    Michele Pagano; Fiscal Year: 2012
    ..We will identify biologically significant substrates of human Fbxo15 (Specific Aim 1) and validate the Fbxo15-dependent regulation of these substrates (Specific Aim 2). ..
  9. Structural studies of substrate recognition and specificity by the SCF ubiquitin
    Bing Hao; Fiscal Year: 2013
    ....
  10. Anti-pancreatic tumorigenesis by inactivation of SAG/RBX2 E3 ubiquitin ligase
    Yi Sun; Fiscal Year: 2013
    ..Our work is, therefore, highly innovative and of significant impact with translational value. ..
  11. Regulation of Innate Immunity by F-Box Proteins
    Beibei Chen; Fiscal Year: 2013
    ....
  12. Septic Lung Injury and Surfactant
    Rama K Mallampalli; Fiscal Year: 2013
    ..Execution of studies outlined in this application will provide a major advance in the conceptual framework for how sepsis causes lung impairment by altering surfactant production. ..
  13. Evolution of Developmental Regulatory Pathways
    Ronald E Ellis; Fiscal Year: 2012
    ..This project will elucidate how the functions of genes change during evolution, which could help scientists choose which creatures to study, and avoid mistaken inferences about their medical significance. ..
  14. Determinants of Protein Degradation Dynamics in Cell Signaling
    BRITNEY LANE MOSS; Fiscal Year: 2013
    ..Thus, this research will both improve basic understanding of mechanisms that drive cancer and aid in designing therapeutics that specifically target dysfunctional signaling pathways in cancer cells. ..
  15. Regulation of Cellular Growth and Division by Ubiquitin-Mediated Proteolysis
    Jennifer A Benanti; Fiscal Year: 2012
    ..We will analyze SCF complex composition in different cell cycle and growth states to address these questions. ..
  16. Global characterization of ubiquitin information networks with mass spectrometry
    Steven P Gygi; Fiscal Year: 2013
    ..Upon completion, our next step will be to create the complementary information networks for human genes. ..
  17. Mechanism of Auxin Action
    MARK A ESTELLE; Fiscal Year: 2012
    ..Defects in the pathway contribute to many disease processes including cancers. This study will advance our understanding of the ubiquitin/proteasome pathway in cell function. ..
  18. The Role of FBXL4 in T-cell Acute Lymphoblastic Leukemia
    JULIE ERIKA M HAYDU; Fiscal Year: 2013
    ..Overall, these studies will characterize the roles and mechanisms of FBXL4 in the pathogenesis of T-ALL. ..
  19. Regulation of cullin-RING ligases by Nedd8
    Raymond J Deshaies; Fiscal Year: 2013
    ....
  20. F-box proteins: deregulated cell cycle control and proteolysis in cancer
    Michele Pagano; Fiscal Year: 2013
    ..As the mechanisms of the ubiquitin-mediated proteolysis of cell cycle regulators are unraveled, this team is committed to the integration of its basic research results with an understanding of malignant transformation. ..
  21. Regulation of Cellular Growth and Division by Ubiquitin-Mediated Proteolysis
    JENNIFER BENANTI; Fiscal Year: 2009
    ..The cell division cycle is regulated by the timed synthesis and destruction of regulatory molecules. Understanding how timed destruction of these molecules occurs will increase our understanding of processes disrupted in cancer cells. ..
  22. MECHANISMS OF CELL CYCLE CONTROL DURING MAMMARY GLAND DE
    Hui Zhang; Fiscal Year: 2001
    ..These studies should also provide a basis to design novel strategies for diagnosis, prognosis, and therapeutic treatment of breast cancers. ..
  23. Phosphoserine Dependant Assembly of Signaling complexes
    Michael Yaffe; Fiscal Year: 2007
    ..unreadable] [unreadable]..
  24. Novel Assays to Identify HIV Vif Inhibitors
    Dana Gabuzda; Fiscal Year: 2006
    ..unreadable] [unreadable] [unreadable] [unreadable]..
  25. Analysis of ASKs, Components of SCF Ubiquitin-Ligases
    DEREK GINGERICH; Fiscal Year: 2005
    ..abstract_text> ..
  26. F box Proteins and Deregulated Proteolysis in Cancer
    Michele Pagano; Fiscal Year: 2005
    ..This will be achieved using specific membrane permeable peptides designed on the basis of our structural and biochemical information. ..
  27. Functional Dissection of an F-box Protein in Development
    Michael Weir; Fiscal Year: 2006
    ..abstract_text> ..
  28. Analysis of Fbx2 Family of Ubiquitin Ligases
    Henry Paulson; Fiscal Year: 2007
    ..In three complementary aims, we will determine whether F box proteins encoded by the Fbx2 gene family function as ubiquitin ligases to mediate glycoprotein quality control in ..
  29. Cell cycle and transcriptional control by F box proteins
    Curt Wittenberg; Fiscal Year: 2005
    ..Understanding these regulatory mechanisms is central to understanding a range of human conditions including cancer, developmental defects and heritable disease. ..
  30. SAG E3 ubiquitin ligase in angiogenesis & carcinogenesis
    Yi Sun; Fiscal Year: 2010
    ..Targeting SAG in cancer cells, via siRNA silencing or small molecule inhibitors, would, therefore, be a valid antianglogenesis therapy. ..
  31. Establishment of C.elegans tissue culture cell lines
    EDWARD KIPREOS; Fiscal Year: 2007
    ..The availability of cell lines would greatly extend research using this organism to provide further health-related insights. [unreadable] [unreadable]..
  32. Protein Knockout Technology/Molecular Analysis of Cancer
    Pengbo Zhou; Fiscal Year: 2004
    ....
  33. Ubiquitin-Proteolytic Control of HOXA9 in Leukemogenesis
    Pengbo Zhou; Fiscal Year: 2010
    ..abstract_text> ..
  34. Substrates of SAG-SCF E3 ligase regulate hypoxia response
    Yi Sun; Fiscal Year: 2007
    ..These initial studies will set the stage for a more detailed investigation of the mechanism of SAG mediated suppression of apoptosis. [unreadable] [unreadable]..
  35. The role of Cyclin E in growth control and tumorogenesis
    Steven Reed; Fiscal Year: 2008
    ..It is hoped that insights gained from understanding these fundamental mechanisms of oncogenesis will lead to new approaches to cancer prevention and therapy. ..
  36. Regulation of Nucleotide Excision Repair by Proteolysis
    Pengbo Zhou; Fiscal Year: 2008
    ..abstract_text> ..
  37. Genetics of Cell Cycle Regulators in C. elegans
    Edward T Kipreos; Fiscal Year: 2010
    ..The abstract has been modified to eliminate the previously proposed screen to identify cullin PTMs. ..
  38. THE S. CEREVISIAE S PHASE CHECKPOINT
    Steven Reed; Fiscal Year: 2003
    ....
  39. Receptor-Mediated Endocytosis of Legionella Pneumophila
    Yousef Abu Kwaik; Fiscal Year: 2004
    ..Our studies may uncover potential pathogenic evolution of Lpn to invade the more evolved mammalian cells, and may contribute to the understanding of invasion of protozoa by Mycobacterium and Chlamydia. ..
  40. Stress proteins in autoimmune depigmentation
    ISABELLE LE POOLE; Fiscal Year: 2005
    ..The same model will be of use to test the efficacy of therapeutic modalities to be developed for vitiligo in the future. ..
  41. Pigmentation and Diversity Conference
    ISABELLE LE POOLE; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable] [unreadable]..
  42. The Pore-forming Toxin of Legionella Pneumophila
    Yousef Abu Kwaik; Fiscal Year: 2003
    ..Our studies on L. pneumophila may provide a paradigm for other vacuolar intracellular pathogens such as Mycobacterium, Salmonella, and Chlamydia. ..
  43. Hedgehog signaling as a novel regulator of hematopoiesis
    Iannis Aifantis; Fiscal Year: 2007
    ..We will complement these experiments with the study of novel Hh activating mouse mutants in which we will define the exact role of the Gli factors in the regulation of mammalian lymphopoiesis and hematopoiesis. ..
  44. Regulation and Function of MAPKAP Kinases
    Thomas Sturgill; Fiscal Year: 2005
    ..Aim four is to characterize the activation, enzymatic properties, and functions of MAPKAP kinase-like enzymes (Rcklp, Rck2p) in yeast, a model eukaryote, using combined biochemical and genetic approaches. ..
  45. BIACORE 3000 Biosensor
    Cecile Pickart; Fiscal Year: 2004
    ..In recognition of this fact, the Bloomberg School of Public Health has made a substantial commitment to the long-term operation and maintenance of the Biacore 3000 ..
  46. GENETIC ANALYSIS OF EARLY LIMB DEVELOPMENT
    Arend Sidow; Fiscal Year: 2004
    ..Because Dac is likely to be the mouse ortholog of the human Split Hand/Foot Malformation 3 gene, this project may also bear direct relevance to understanding and diagnosis of congenital limb diseases. ..
  47. ASCB Conf:Nontraditional Functions of Ubiquitin and UbLs
    Cecile Pickart; Fiscal Year: 2002
    ..There will also be a poster session. The format of the Conference, and its small size, are designed to foster interactions among the 200 participants. ..
  48. Genistein induces thymic atrophy: a health concern?
    Paul Cooke; Fiscal Year: 2006
    ..These studies will advance our understanding of isoflavone effects on the immune system, and also may have relevance for soy-fed infants and laboratory rodents consuming soy-based feed. ..
  49. The ProPhylER Database and Web Resource
    Arend Sidow; Fiscal Year: 2006
    ..unreadable] [unreadable]..
  50. Autoimmune vitiligo as a roadmap to melanoma therapy
    ISABELLE LE POOLE; Fiscal Year: 2007
    ..Importantly, the cloning of high affinity T cell receptors in retroviral vectors may be suitable for introduction into patient PBL for treatment of malignant melanoma. ..
  51. The Ciona savignyi Genetic Map
    Arend Sidow; Fiscal Year: 2008
    ..Insights into the molecular mechanisms of regulation and development using Ciona as a model are highly effective and relevant to the homologous processes in human. ..
  52. Chemopreventive treatment of familial melanoma
    ISABELLE LE POOLE; Fiscal Year: 2008
    ..3] To quantify melanoma tumor growth and measure immunologic parameters (cytokine secretion by ELISA and ELISPOT) in mice treated with bleaching agents and IL-2. [unreadable] [unreadable] [unreadable]..
  53. Regulation of interferon receptor by Leishmania kinase
    SERGE FUCHS; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable]..
  54. Role of the Archipelago gene in Drosophila tracheal morphogenesis
    Kenneth H Moberg; Fiscal Year: 2010
    ..Thus, we hypothesize that ago plays an important role in the homeostatic mechanisms that restrain tracheal branching. Our goal in Specific Aim 3 is to define this role and elucidate its molecular basis. ..
  55. Molecular pathogenesis of Francisella tularnesis
    YOUSEF A ABU KWAIK; Fiscal Year: 2010
    ..The bacterial effectors involved in exploiting the macrophage are potential targets for treatment as well as potential vaccine candidates. ..
  56. Interaction of auxin and abscisic acid signaling
    LUCIA STRADER; Fiscal Year: 2007
    ..By studying and cloning suppresors, as well as identifying IBR5 substrates, a more in-depth understanding of auxin and ABA cross-talk will be gained. ..
  57. Stability of prolactin receptor and prolactin signaling
    Serge Y Fuchs; Fiscal Year: 2010
    ....
  58. CELL CYCLE ARREST AND SIGNAL TRANSDUCTION IN YEAST
    ELAINE ELION; Fiscal Year: 2009
    ..abstract_text> ..
  59. mTOR Signaling Pathways
    Thomas W Sturgill; Fiscal Year: 2010
    ..We will investigate novel candidate mTOR-interacting proteins identified by MS. Finally, to understand better the mechanisms involved in mTORC2, we propose to identify pianissimo-interacting proteins. ..
  60. Skyscan 1172 ex-vivo microComputed Tomography System
    Francesco Ramirez; Fiscal Year: 2007
    ..Acquisition of this equipment will enable our institutions to engage in biomedical research highly relevant to pathophysiological processes and animal models of human diseases. [unreadable] [unreadable] [unreadable]..
  61. A transgenic model of ocular inflammation
    Russell Van Gelder; Fiscal Year: 2007
    ..unreadable] [unreadable]..
  62. DEVELOPMENTAL BIOLOGY AND GENETICS OF THE MAIZE LEAF
    Michael Freeling; Fiscal Year: 2001
    ..We are elucidating a molecular genetic basis for heterochrony, the prevailing theory that links evolution with developmental biology. ..