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 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
  2. 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
  3. 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
  4. 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
  5. 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
  6. 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
  7. 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
  8. 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
  9. 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
  10. 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

Detail Information

Publications238 found, 100 shown here

  1. 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...
  2. 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...
  3. 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...
  4. 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...
  5. 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...
  6. 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...
  7. 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...
  8. 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...
  9. 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...
  10. 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...
  11. 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...
  12. 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...
  13. pmc Systematic analysis and nomenclature of mammalian F-box proteins
    Jianping Jin
    Genes Dev 18:2573-80. 2004
  14. 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...
  15. 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...
  16. 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...
  17. 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...
  18. 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...
  19. 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...
  20. 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...
  21. 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
    ....
  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 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
    ....
  24. 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...
  25. 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...
  26. 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...
  27. 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...
  28. 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...
  29. 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...
  30. 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...
  31. 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...
  32. 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...
  33. 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...
  34. 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...
  35. 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...
  36. 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
    ....
  37. 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...
  38. 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...
  39. 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...
  40. 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
    ....
  41. 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...
  42. 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...
  43. 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...
  44. 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...
  45. 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...
  46. 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...
  47. 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...
  48. 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...
  49. 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...
  50. 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.
  51. 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...
  52. 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
    ....
  53. 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
    ....
  54. 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...
  55. 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...
  56. 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...
  57. 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...
  58. doi 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...
  59. 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...
  60. 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...
  61. 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...
  62. 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...
  63. 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...
  64. 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...
  65. 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
    ....
  66. 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...
  67. 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...
  68. 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...
  69. 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...
  70. 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...
  71. 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...
  72. 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...
  73. 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...
  74. 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...
  75. 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...
  76. 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...
  77. 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
    ....
  78. 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...
  79. 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...
  80. 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...
  81. 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...
  82. 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...
  83. 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...
  84. 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...
  85. 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...
  86. 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...
  87. 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...
  88. 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...
  89. ncbi Overexpression of Arabidopsis thaliana SKP1 homologues in yeast inactivates the Mig1 repressor by destabilising the F-box protein Grr1
    J Schouten
    Institute of Molecular Plant Sciences, Leiden University, Clusius Laboratory, The Netherlands
    Mol Gen Genet 263:309-19. 2000
    ..Our results suggest that the plant counterpart of yeast Skp1 is probably also instrumental in ubiquitin-mediated proteolysis of specific proteins via an SCF-like pathway...
  90. pmc FBXO11 promotes the Neddylation of p53 and inhibits its transcriptional activity
    Wassim M Abida
    Institute for Cancer Genetics and the Department of Pathology, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA
    J Biol Chem 282:1797-804. 2007
    ..Our study provides an example of an F-box protein acting as an adaptor protein that can mediate the neddylation of a non-cullin substrate...
  91. pmc Cdc53/cullin and the essential Hrt1 RING-H2 subunit of SCF define a ubiquitin ligase module that activates the E2 enzyme Cdc34
    J H Seol
    Division of Biology, California Institute of Technology, Pasadena, California 91125, USA
    Genes Dev 13:1614-26. 1999
    ..We conclude that Cdc53/Hrt1 comprise a highly conserved module that serves as the functional core of a broad variety of heteromeric ubiquitin ligases...
  92. pmc Cdc34 and the F-box protein Met30 are required for degradation of the Cdk-inhibitory kinase Swe1
    P Kaiser
    The Scripps Research Institute TSRI, La Jolla, California 92037 USA
    Genes Dev 12:2587-97. 1998
    ..Our data, in combination with previously published results, also provide evidence for distinct SCF complexes in vivo and support the idea that their F-box subunits mediate SCF substrate specificity...
  93. pmc The yeast ubiquitin ligase SCFMet30 regulates heavy metal response
    James L Yen
    Department of Biological Chemistry, School of Medicine, University of California Irvine, 92697 1700, USA
    Mol Biol Cell 16:1872-82. 2005
    ..Genetic analyses demonstrated a complex effect of cadmium on cell cycle regulation that might be important to safeguard cellular and genetic integrity when cells are exposed to heavy metals...
  94. pmc Transferable domain in the G(1) cyclin Cln2 sufficient to switch degradation of Sic1 from the E3 ubiquitin ligase SCF(Cdc4) to SCF(Grr1)
    Catherine Berset
    Department of Molecular and Medical Genetics, Oregon Health and Science University, Portland, Oregon 97201, USA
    Mol Cell Biol 22:4463-76. 2002
    ..In summary, we have identified a small transferable domain in Cln2 that can redirect a stabilized SCF(Cdc4) target for SCF(Grr1)-mediated degradation by the ubiquitin-proteasome pathway...
  95. pmc Phosphorylation controls timing of Cdc6p destruction: A biochemical analysis
    S Elsasser
    Braun Laboratories, California Institute of Technology, Pasadena, California 91125, USA
    Mol Biol Cell 10:3263-77. 1999
    ..However, stabilization through mutation of three N-terminal phosphorylation sites or of the single C-terminal phosphorylation site leads to dominant lethality when combined with certain mutations in the anaphase-promoting complex...
  96. ncbi Signal transduction. Signaling specificity in yeast
    Elaine A Elion
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA
    Science 307:687-8. 2005
  97. 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...
  98. 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...
  99. pmc Cic1, an adaptor protein specifically linking the 26S proteasome to its substrate, the SCF component Cdc4
    S Jager
    Institut für Biochemie der Universität Stuttgart, Pfaffenwaldring 55, D 70569 Stuttgart, Germany
    EMBO J 20:4423-31. 2001
    ..Cic1 interacts in vitro and in vivo with Cdc4, suggesting a function as a new kind of substrate recruiting factor or adaptor associated with the proteasome...
  100. ncbi In vitro reconstitution of SCF substrate ubiquitination with purified proteins
    Matthew D Petroski
    Howard Hughes Medical Institute, Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA
    Methods Enzymol 398:143-58. 2005
    ..Based on our experience in reconstituting Sic1 ubiquitination, we suggest some parameters to consider that should be generally applicable to the study of different SCF complexes and other ubiquitin ligases...
  101. pmc Distinct mechanisms control the stability of the related S-phase cyclins Clb5 and Clb6
    Leisa P Jackson
    DCMB Group, Department of Biology, Box 91000, LSRC Bldg, Research Dr, Durham, NC 27708, USA
    Mol Cell Biol 26:2456-66. 2006
    ..Taken together, these findings suggest that the SCF(Cdc4) ubiquitin ligase complex regulates Clb6 turnover and that the functional differences exhibited by Clb5 and Clb6 arise from the distinct mechanisms controlling their stability...

Research Grants80

  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. Roles of the Checkpoint Kinase Chk1 in Cancer Biology and Therapy
    You Wei Zhang; Fiscal Year: 2007
    ....
  3. F-box proteins: deregulated cell cycle control and proteolysis in cancer
    Michele Pagano; Fiscal Year: 2010
    ..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. ..
  4. F-box proteins: deregulated cell cycle control and proteolysis in cancer
    Michele Pagano; Fiscal Year: 2007
    ..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. ..
  5. F-box proteins: deregulated cell cycle control and proteolysis in cancer
    Michele Pagano; Fiscal Year: 2009
    ..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. ..
  6. F-box proteins: deregulated cell cycle control and proteolysis in cancer
    Michele Pagano; Fiscal Year: 2006
    ..unreadable] [unreadable] [unreadable]..
  7. Regulation of neural development by F-box mediated ubiquitination
    ELENA M CASEY; Fiscal Year: 2010
    ..This application will address how the levels of proteins are controlled by degradation to ensure ordered progression through neurogenesis and therefore the proper development of the central nervous system. ..
  8. Regulation of the cell cycle by SCF and APC/C ubiquitin ligases
    Michele Pagano; Fiscal Year: 2009
    ..It is anticipated that the results of our studies will have an impact on both basic science and cancer biology. ..
  9. Regulation of the cell cycle by SCF and APC/C ubiquitin ligases
    Michele Pagano; Fiscal Year: 2006
    ..It is anticipated that the results of our studies will have an impact on both basic science and cancer biology. ..
  10. Regulation of the cell cycle by SCF and APC/C ubiquitin ligases
    Michele Pagano; Fiscal Year: 2007
    ..It is anticipated that the results of our studies will have an impact on both basic science and cancer biology. ..
  11. Regulation of the cell cycle by SCF and APC/C ubiquitin ligases
    Michele Pagano; Fiscal Year: 2006
    ..It is anticipated that the results of our studies will have an impact on both basic science and cancer biology. ..
  12. 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. ..
  13. MECHANISMS OF CELL CYCLE CONTROL DURING MAMMARY GLAND DE
    Hui Zhang; Fiscal Year: 2000
    ..These studies should also provide a basis to design novel strategies for diagnosis, prognosis, and therapeutic treatment of breast cancers. ..
  14. A NOVEL F BOX PROTEIN REGULATING MITOSIS
    Peter Jackson; Fiscal Year: 2002
    ..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. ..
  15. A NOVEL F BOX PROTEIN REGULATING MITOSIS
    Peter Jackson; Fiscal Year: 2002
    ..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. ..
  16. A NOVEL F BOX PROTEIN REGULATING MITOSIS
    Peter Jackson; Fiscal Year: 2001
    ..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. ..
  17. A NOVEL F BOX PROTEIN REGULATING MITOSIS
    Peter Jackson; Fiscal Year: 2003
    ..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. ..
  18. A NOVEL F BOX PROTEIN REGULATING MITOSIS
    Peter Jackson; Fiscal Year: 2001
    ..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. ..
  19. 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. ..
  20. Roles of the Checkpoint Kinase Chk1 in Cancer Biology and Therapy
    You Wei Zhang; Fiscal Year: 2009
    ....
  21. Roles of the Checkpoint Kinase Chk1 in Cancer Biology and Therapy
    You Wei Zhang; Fiscal Year: 2010
    ....
  22. CELL CYCLE GENES AND CELLULAR SENESCENCE AND AGING
    Jeffrey Harper; Fiscal Year: 2000
    ....
  23. CELL CYCLE GENES AND CELLULAR SENESCENCE AND AGING
    Jeffrey Harper; Fiscal Year: 1999
    ....
  24. CELL CYCLE GENES AND CELLULAR SENESCENCE AND AGING
    Jeffrey Harper; Fiscal Year: 2001
    ....
  25. Regulation of the G1 Phase by the Ubiquitin Pathway
    Michele Pagano; Fiscal Year: 2003
    ..Under Aim 3, the principal investigator will also clone and characterize three proteins that he has found associated specifically with Fb13 in vivo. ..
  26. Regulation of the G1 Phase by the Ubiquitin Pathway
    Michele Pagano; Fiscal Year: 2004
    ..Under Aim 3, the principal investigator will also clone and characterize three proteins that he has found associated specifically with Fb13 in vivo. ..
  27. Regulation of the G1 Phase by the Ubiquitin Pathway
    Michele Pagano; Fiscal Year: 2002
    ..Under Aim 3, the principal investigator will also clone and characterize three proteins that he has found associated specifically with Fb13 in vivo. ..
  28. Regulation of the G1 Phase by the Ubiquitin Pathway
    Michele Pagano; Fiscal Year: 2005
    ..Under Aim 3, the principal investigator will also clone and characterize three proteins that he has found associated specifically with Fb13 in vivo. ..
  29. Regulation of the G1 Phase by the Ubiquitin Pathway
    Michele Pagano; Fiscal Year: 2003
    ..Under Aim 3, the principal investigator will also clone and characterize three proteins that he has found associated specifically with Fb13 in vivo. ..
  30. Mechanism of SAG apoptosis protection under hypoxia
    Yi Sun; Fiscal Year: 2005
    ....
  31. Mechanism of SAG apoptosis protection under hypoxia
    Yi Sun; Fiscal Year: 2007
    ....
  32. 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. ..
  33. Mechanism of SAG apoptosis protection under hypoxia
    Yi Sun; Fiscal Year: 2006
    ....
  34. SAG E3 ubiquitin ligase in angiogenesis & carcinogenesis
    Yi Sun; Fiscal Year: 2009
    ..Targeting SAG in cancer cells, via siRNA silencing or small molecule inhibitors, would, therefore, be a valid antianglogenesis therapy. ..
  35. Mechanism of Auxin Action
    MARK A ESTELLE; Fiscal Year: 2010
    ..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. ..
  36. Mechanism of Auxin Action
    Mark Estelle; Fiscal Year: 2009
    ..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. ..
  37. Substrates of SAG-SCF E3 ligase regulate hypoxia response
    Yi Sun; Fiscal Year: 2006
    ..These initial studies will set the stage for a more detailed investigation of the mechanism of SAG mediated suppression of apoptosis. [unreadable] [unreadable]..
  38. 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]..
  39. Phosphoserine Dependant Assembly of Signaling complexes
    Michael Yaffe; Fiscal Year: 2004
    ....
  40. Phosphoserine Dependant Assembly of Signaling complexes
    Michael Yaffe; Fiscal Year: 2007
    ..unreadable] [unreadable]..
  41. Phosphoserine Dependant Assembly of Signaling complexes
    Michael Yaffe; Fiscal Year: 2006
    ..unreadable] [unreadable]..
  42. Phosphoserine Dependant Assembly of Signaling complexes
    Michael Yaffe; Fiscal Year: 2005
    ....
  43. Mechanisms of SAG Inhibition of Carcinogenesis & Apoptosis
    Yi Sun; Fiscal Year: 2007
    ..Furthermore, we will provide a molecular basis for future screening of drugs that may act as chemo-prevention agents via SAG induction. ..
  44. Mechanisms of SAG Inhibition of Carcinogenesis & Apoptosis
    Yi Sun; Fiscal Year: 2009
    ..Furthermore, we will provide a molecular basis for future screening of drugs that may act as chemo-prevention agents via SAG induction. ..
  45. Mechanisms of SAG Inhibition of Carcinogenesis & Apoptosis
    Yi Sun; Fiscal Year: 2010
    ..Furthermore, we will provide a molecular basis for future screening of drugs that may act as chemo-prevention agents via SAG induction. ..
  46. Mechanisms of SAG Inhibition of Carcinogenesis & Apoptosis
    Yi Sun; Fiscal Year: 2006
    ..Furthermore, we will provide a molecular basis for future screening of drugs that may act as chemo-prevention agents via SAG induction. ..
  47. CLOCK MECHANISM UNDERLYING DROSOPHILA RHYTHMIC BEHAVIOR
    Isaac Edery; Fiscal Year: 2006
    ..This could be particularly rewarding in the case of Slimb and its mammalian homolog beta-TrCP, which recognize a variety of phosphotargets and have important roles in development, apoptosis, inflammatory responses and cancer. ..
  48. Regulation of Cellular Growth and Division by Ubiquitin-Mediated Proteolysis
    Jennifer A Benanti; Fiscal Year: 2010
    ..We will analyze SCF complex composition in different cell cycle and growth states to address these questions. ..
  49. CLOCK MECHANISM UNDERLYING DROSOPHILA RHYTHMIC BEHAVIOR
    Isaac Edery; Fiscal Year: 2004
    ..This could be particularly rewarding in the case of Slimb and its mammalian homolog beta-TrCP, which recognize a variety of phosphotargets and have important roles in development, apoptosis, inflammatory responses and cancer. ..
  50. CLOCK MECHANISM UNDERLYING DROSOPHILA RHYTHMIC BEHAVIOR
    Isaac Edery; Fiscal Year: 2005
    ..This could be particularly rewarding in the case of Slimb and its mammalian homolog beta-TrCP, which recognize a variety of phosphotargets and have important roles in development, apoptosis, inflammatory responses and cancer. ..
  51. CLOCK MECHANISM UNDERLYING DROSOPHILA RHYTHMIC BEHAVIOR
    Isaac Edery; Fiscal Year: 2007
    ..This could be particularly rewarding in the case of Slimb and its mammalian homolog beta-TrCP, which recognize a variety of phosphotargets and have important roles in development, apoptosis, inflammatory responses and cancer. ..
  52. Septic Lung Injury and Surfactant
    Rama K Mallampalli; Fiscal Year: 2010
    ..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. ..
  53. Mechanisms of tumor suppression by Fbw7
    Jonathan Grim; Fiscal Year: 2009
    ..As such, it is a crucial step towards developing treatment strategies for tumors associated with this pathway. ..
  54. Mechanisms of tumor suppression by Fbw7
    Jonathan Grim; Fiscal Year: 2007
    ..As such, it is a crucial step towards developing treatment strategies for tumors associated with this pathway. ..
  55. 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. ..
  56. Mechanisms of tumor suppression by Fbw7
    Jonathan Grim; Fiscal Year: 2006
    ..As such, it is a crucial step towards developing treatment strategies for tumors associated with this pathway. ..
  57. Mechanisms of tumor suppression by Fbw7
    Jonathan Grim; Fiscal Year: 2009
    ..As such, it is a crucial step towards developing treatment strategies for tumors associated with this pathway. ..
  58. Novel Substrates of SCF Ubiquitin Ligases in Cell Cycle Control and Cancer
    Michele Pagano; Fiscal Year: 2007
    ..Therefore, the information gained from the proposed studies will be of direct relevance to cancer biology and other proliferative diseases. [unreadable] [unreadable] [unreadable]..
  59. CELL CYCLE CONTROL OF PROTEOLYSIS BY F-BOX PROTEINS
    Dieter Wolf; Fiscal Year: 1999
    ..In the future, this knowledge may support the design of compounds that specifically interfere with aspects of SCF functions involved in tumor development and progression. ..
  60. CELL CYCLE CONTROL OF PROTEOLYSIS BY F-BOX PROTEINS
    Dieter Wolf; Fiscal Year: 2001
    ..In the future, this knowledge may support the design of compounds that specifically interfere with aspects of SCF functions involved in tumor development and progression. ..
  61. CELL CYCLE CONTROL OF PROTEOLYSIS BY F-BOX PROTEINS
    Dieter Wolf; Fiscal Year: 2000
    ..In the future, this knowledge may support the design of compounds that specifically interfere with aspects of SCF functions involved in tumor development and progression. ..
  62. CELL CYCLE CONTROL OF PROTEOLYSIS BY F-BOX PROTEINS
    Dieter Wolf; Fiscal Year: 2003
    ..In the future, this knowledge may support the design of compounds that specifically interfere with aspects of SCF functions involved in tumor development and progression. ..
  63. CELL CYCLE CONTROL OF PROTEOLYSIS BY F-BOX PROTEINS
    Dieter Wolf; Fiscal Year: 2002
    ..In the future, this knowledge may support the design of compounds that specifically interfere with aspects of SCF functions involved in tumor development and progression. ..
  64. Novel Assays to Identify HIV Vif Inhibitors
    Dana Gabuzda; Fiscal Year: 2005
    ..By this multidisciplinary approach, these studies will provide novel insights into biological processes relevant for Vif function during HIV replication and will also facilitate antiviral drug discovery for HIV/AIDS. ..
  65. Analysis of ASKs, Components of SCF Ubiquitin-Ligases
    DEREK GINGERICH; Fiscal Year: 2003
    ..abstract_text> ..
  66. Novel Assays to Identify HIV Vif Inhibitors
    Dana Gabuzda; Fiscal Year: 2006
    ..unreadable] [unreadable] [unreadable] [unreadable]..
  67. Analysis of ASKs, Components of SCF Ubiquitin-Ligases
    DEREK GINGERICH; Fiscal Year: 2004
    ..abstract_text> ..
  68. Analysis of ASKs, Components of SCF Ubiquitin-Ligases
    DEREK GINGERICH; Fiscal Year: 2005
    ..abstract_text> ..
  69. 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. ..
  70. F box Proteins and Deregulated Proteolysis in Cancer
    Michele Pagano; Fiscal Year: 2003
    ..This will be achieved using specific membrane permeable peptides designed on the basis of our structural and biochemical information. ..
  71. Functional Dissection of an F-box Protein in Development
    Michael Weir; Fiscal Year: 2006
    ..abstract_text> ..
  72. F box Proteins and Deregulated Proteolysis in Cancer
    Michele Pagano; Fiscal Year: 2001
    ..This will be achieved using specific membrane permeable peptides designed on the basis of our structural and biochemical information. ..
  73. Functional Dissection of an F-box Protein in Development
    Michael Weir; Fiscal Year: 2004
    ..abstract_text> ..
  74. F box Proteins and Deregulated Proteolysis in Cancer
    Michele Pagano; Fiscal Year: 2002
    ..This will be achieved using specific membrane permeable peptides designed on the basis of our structural and biochemical information. ..
  75. F box Proteins and Deregulated Proteolysis in Cancer
    Michele Pagano; Fiscal Year: 2004
    ..This will be achieved using specific membrane permeable peptides designed on the basis of our structural and biochemical information. ..
  76. Functional Dissection of an F-box Protein in Development
    Michael Weir; Fiscal Year: 2002
    ..abstract_text> ..
  77. F box Proteins and Deregulated Proteolysis in Cancer
    Michele Pagano; Fiscal Year: 2002
    ..This will be achieved using specific membrane permeable peptides designed on the basis of our structural and biochemical information. ..
  78. Functional Dissection of an F-box Protein in Development
    Michael Weir; Fiscal Year: 2003
    ..abstract_text> ..
  79. 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. ..
  80. Analysis of Fbx2 Family of Ubiquitin Ligases
    Henry Paulson; Fiscal Year: 2006
    ..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 ..