CDC4

Summary

Gene Symbol: CDC4
Description: SCF ubiquitin ligase complex subunit CDC4
Species: Saccharomyces cerevisiae S288c

Top Publications

  1. 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
  2. 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
  3. ncbi Reconstitution of G1 cyclin ubiquitination with complexes containing SCFGrr1 and Rbx1
    D Skowyra
    Verna and Marrs McLean Department of Biochemistry, Howard Hughes Medical Institute, Baylor College of Medicine, Houston, TX 77030, USA
    Science 284:662-5. 1999
  4. pmc The SCFCdc4 ubiquitin ligase regulates calcineurin signaling through degradation of phosphorylated Rcn1, an inhibitor of calcineurin
    Tsutomu Kishi
    Kishi Initiative Research Unit, RIKEN, 2 1 Hirosawa, Wako, Saitama 351 0198, Japan
    Proc Natl Acad Sci U S A 104:17418-23. 2007
  5. pmc SCFCdc4 enables mating type switching in yeast by cyclin-dependent kinase-mediated elimination of the Ash1 transcriptional repressor
    Qingquan Liu
    School of Biological Sciences, University of Edinburgh, Mayfield Road, Edinburgh EH9 3JR, United Kingdom
    Mol Cell Biol 31:584-98. 2011
  6. ncbi Genome-wide surveys for phosphorylation-dependent substrates of SCF ubiquitin ligases
    Xiaojing Tang
    Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, USA
    Methods Enzymol 399:433-58. 2005
  7. pmc Cdc4, a protein required for the onset of S phase, serves an essential function during G(2)/M transition in Saccharomyces cerevisiae
    P Y Goh
    Institute of Molecular and Cell Biology, Singapore 117609, Singapore
    Mol Cell Biol 19:5512-22. 1999
  8. pmc Composite low affinity interactions dictate recognition of the cyclin-dependent kinase inhibitor Sic1 by the SCFCdc4 ubiquitin ligase
    Xiaojing Tang
    Center for Systems Biology, Samuel Lunenfeld Research Institute, Toronto, ON, Canada M5G 1X5
    Proc Natl Acad Sci U S A 109:3287-92. 2012
  9. 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
  10. 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

Research Grants

  1. How do cyclins drive the cell cycle?
    Frederick R Cross; Fiscal Year: 2010

Scientific Experts

  • Tsutomu Kishi
  • D Lydall
  • Matthew D Petroski
  • FREDERICK CROSS
  • Mike Tyers
  • Stephen Orlicky
  • Xiaojing Tang
  • Frank Sicheri
  • Tanja Mittag
  • Julie D Forman-Kay
  • Qingquan Liu
  • Lan Huang
  • Dorota Skowyra
  • Raymond J Deshaies
  • D Skowyra
  • Hao Huang
  • Neda Delgoshaie
  • Satoru Mimura
  • Nicholas A Lyons
  • Jillian H Hurst
  • Andrew Willems
  • James L Yen
  • Benjamin D Landry
  • Henrik G Dohlman
  • Peter Kaiser
  • Karin Flick
  • Ikram Ouni
  • Alexandre Vendrell
  • R J Deshaies
  • Mariam Aghajan
  • Daniel C Scott
  • Mark K Chee
  • Martin Sadowski
  • M Blondel
  • J W Harper
  • S J Elledge
  • Marie Z Bao
  • Steven D Cappell
  • Mitsunori Kato
  • Tony Pawson
  • Lucy S Drury
  • Rati Verma
  • Hong Lin
  • Jessica McLellan
  • Sohum Mehta
  • Yuan Liu
  • N Mathias
  • Aydin Haririnia
  • Steven B Haase
  • Brenda A Schulman
  • Ning Zheng
  • M Tyers
  • Mikael Borg
  • Bing Hao
  • K Matthew Scaglione
  • Rasanjala Weerasekera
  • Bhupinder Pal
  • Katsumi Kitagawa
  • John F X Diffley
  • Yelena Ivantsiv
  • Leisa P Jackson
  • Alexi Kiss
  • Noriko Kondo-Okamoto
  • Andrew E Deffenbaugh
  • Nikola P Pavletich
  • R M Feldman
  • Regine Barbey
  • Shalon E Babbitt
  • Ti Li
  • G Perkins
  • S Elsasser
  • Song Chou
  • Y Chi
  • Bart M Kus
  • T Kamura
  • K Nasmyth
  • Cheryl Dixon
  • A R Willems
  • L S Drury
  • Gregory A Cope
  • Anne Marinier
  • Pankaj Garg
  • C C Correll
  • Zhifeng Cui
  • Amy Ziemba
  • Gary Kleiger
  • Alain Verreault
  • Adam D Rudner
  • Serge Plamondon
  • Sachdev Sidhu

Detail Information

Publications82

  1. 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...
  2. 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
    ..Hrt1 assembles into recombinant SCF complexes and individually binds Cdc4, Cdc53 and Cdc34, but not Skp1...
  3. ncbi Reconstitution of G1 cyclin ubiquitination with complexes containing SCFGrr1 and Rbx1
    D Skowyra
    Verna and Marrs McLean Department of Biochemistry, Howard Hughes Medical Institute, Baylor College of Medicine, Houston, TX 77030, USA
    Science 284:662-5. 1999
    ..Rbx1, which is also a component of the von Hippel-Lindau tumor suppressor complex, may define a previously unrecognized class of E3-associated proteins...
  4. pmc The SCFCdc4 ubiquitin ligase regulates calcineurin signaling through degradation of phosphorylated Rcn1, an inhibitor of calcineurin
    Tsutomu Kishi
    Kishi Initiative Research Unit, RIKEN, 2 1 Hirosawa, Wako, Saitama 351 0198, Japan
    Proc Natl Acad Sci U S A 104:17418-23. 2007
    ..Here we show that phosphorylation of yeast RCN, Rcn1, triggers degradation through the SCF(Cdc4) ubiquitin ligase complex...
  5. pmc SCFCdc4 enables mating type switching in yeast by cyclin-dependent kinase-mediated elimination of the Ash1 transcriptional repressor
    Qingquan Liu
    School of Biological Sciences, University of Edinburgh, Mayfield Road, Edinburgh EH9 3JR, United Kingdom
    Mol Cell Biol 31:584-98. 2011
    ..Here, we report that the ubiquitin ligase SCF(Cdc4) mediates the phosphorylation-dependent elimination of Ash1...
  6. ncbi Genome-wide surveys for phosphorylation-dependent substrates of SCF ubiquitin ligases
    Xiaojing Tang
    Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, USA
    Methods Enzymol 399:433-58. 2005
    ..The archetype for such interactions is the binding of the yeast F-box protein Cdc4 to its various substrates by means of multiple motifs that weakly match an optimal consensus called the Cdc4 ..
  7. pmc Cdc4, a protein required for the onset of S phase, serves an essential function during G(2)/M transition in Saccharomyces cerevisiae
    P Y Goh
    Institute of Molecular and Cell Biology, Singapore 117609, Singapore
    Mol Cell Biol 19:5512-22. 1999
    Saccharomyces cerevisiae proteins Cdc4 and Cdc20 contain WD40 repeats and participate in proteolytic processes...
  8. pmc Composite low affinity interactions dictate recognition of the cyclin-dependent kinase inhibitor Sic1 by the SCFCdc4 ubiquitin ligase
    Xiaojing Tang
    Center for Systems Biology, Samuel Lunenfeld Research Institute, Toronto, ON, Canada M5G 1X5
    Proc Natl Acad Sci U S A 109:3287-92. 2012
    The ubiquitin ligase SCF(Cdc4) (Skp1/Cul1/F-box protein) recognizes its substrate, the cyclin-dependent kinase inhibitor Sic1, in a multisite phosphorylation-dependent manner...
  9. 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
    ..WD40 repeat F box proteins, such as Cdc4 and beta-TrCP, contain a conserved dimerization motif called the D domain...
  10. 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
    ..The F-box protein Cdc4 captures phosphorylated forms of the cyclin-dependent kinase inhibitor Sic1 for ubiquitination in late G1 phase, an ..
  11. pmc SCFCdc4-mediated degradation of the Hac1p transcription factor regulates the unfolded protein response in Saccharomyces cerevisiae
    Bhupinder Pal
    Department of Biochemistry and Molecular Biology, University of Melbourne, Victoria 3010, Australia
    Mol Biol Cell 18:426-40. 2007
    ..that degradation of Hac1p by the proteasome involves the E2 ubiquitin-conjugating enzyme Ubc3/Cdc34p and the SCF(Cdc4) E3 complex...
  12. 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
    ..Skp1, Cdc53, and the F-box protein Cdc4 form a complex, SCFCdc4, which functions as a Sic1 ubiquitin-ligase (E3) in combination with the ubiquitin ..
  13. pmc The Cdc4/34/53 pathway targets Cdc6p for proteolysis in budding yeast
    L S Drury
    Imperial Cancer Research Fund, Clare Hall Laboratories, South Mimms EN6 3LD, UK
    EMBO J 16:5966-76. 1997
    ..Likewise, mutations in the Cdc4/34/53 pathway involved in ubiquitin-mediated degradation block proteolysis and genetic evidence is presented ..
  14. 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
    ..Genetic data suggest that SIC1 proteolysis is mediated by the ubiquitin pathway and requires the action of CDC34, CDC4, CDC53, SKP1, and CLN/CDC28...
  15. pmc Cdc53p acts in concert with Cdc4p and Cdc34p to control the G1-to-S-phase transition and identifies a conserved family of proteins
    N Mathias
    Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis 46202 5122, USA
    Mol Cell Biol 16:6634-43. 1996
    ..During G1, CDC4, encoding a WD-40 repeat protein, and CDC34, encoding a ubiquitin-conjugating enzyme, are involved in the ..
  16. pmc The transcription factor Swi5 regulates expression of the cyclin kinase inhibitor p40SIC1
    D Knapp
    Research Institute of Molecular Pathology, Vienna, Austria
    Mol Cell Biol 16:5701-7. 1996
    ..inhibitor p40SIC1 in late G1, which is mediated by the ubiquitin-conjugating enzyme Cdc34 and two other proteins, Cdc4 and Cdc53...
  17. 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
    We have identified the yeast and human homologs of the SKP1 gene as a suppressor of cdc4 mutants and as a cyclin F-binding protein...
  18. ncbi The B-type cyclin kinase inhibitor p40SIC1 controls the G1 to S transition in S. cerevisiae
    E Schwob
    I M P Research Institute of Molecular Pathology, Vienna, Austria
    Cell 79:233-44. 1994
    ..In wild-type cells, p40SIC1 protein appears at the end of mitosis and disappears shortly before S phase. Proteolysis of a cyclin-specific inhibitor of Cdc28 is therefore an essential aspect of the G1 to S phase transition...
  19. pmc Multisite phosphorylation of the Saccharomyces cerevisiae filamentous growth regulator Tec1 is required for its recognition by the E3 ubiquitin ligase adaptor Cdc4 and its subsequent destruction in vivo
    Marie Z Bao
    Department of Biochemistry and Biophysics, University of California, 600 16th St, MC2200, San Francisco, CA 94158 2200, USA
    Eukaryot Cell 9:31-6. 2010
    ..T273 is embedded in the sequence LLpTP, which is identical to the canonical binding site for Cdc4, a conserved F-box substrate adaptor for the SCF complex...
  20. 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
    ..Biochemical data indicate that the closely related yeast SCF(Cdc4) complex recognizes the multisite phosphorylated Sic1 substrate similarly and identify three doubly phosphorylated ..
  21. pmc Nuclear-specific degradation of Far1 is controlled by the localization of the F-box protein Cdc4
    M Blondel
    Swiss Institute for Experimental Cancer Research ISREC, Chemin des Boveresses 155, 1066 Epalinges VD, Institute of Biochemistry, University of Lausanne UNIL, Chemin des Boveresses 155, 1066 Epalinges VD, Switzerland
    EMBO J 19:6085-97. 2000
    ..Here we show that SCF(Cdc4) ubiquitylates Far1 in the nucleus, which in turn targets the multi-ubiquitylated protein to 26S proteasomes most ..
  22. pmc SCF E3-mediated autoubiquitination negatively regulates activity of Cdc34 E2 but plays a nonessential role in the catalytic cycle in vitro and in vivo
    K Matthew Scaglione
    Edward A Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, St Louis, MO 63104, USA
    Mol Cell Biol 27:5860-70. 2007
    ..as the lysineless (K0)Cdc34(DeltaC) is indistinguishable from Cdc34(DeltaC) in ubiquitination of the prototype SCF(Cdc4) substrate Sic1 in vitro, and replacement of the CDC34 gene with either the (K0)cdc34(DeltaC) or the cdc34(DeltaC) ..
  23. pmc Unique role for the UbL-UbA protein Ddi1 in turnover of SCFUfo1 complexes
    Yelena Ivantsiv
    Department of Life Sciences, Ben Gurion University of the Negev, Beersheba 84105, Israel
    Mol Cell Biol 26:1579-88. 2006
    ..These results imply a role for the UIMs in turnover of SCF(Ufo1) complexes that is dependent on Ddi1, a novel activity for an UbL-UbA protein...
  24. pmc Regulation of the histone deacetylase Hst3 by cyclin-dependent kinases and the ubiquitin ligase SCFCdc4
    Neda Delgoshaie
    From the Institute for Research in Immunology and Cancer, Universite de Montreal, Succursale Centre Ville, Montreal, Quebec H3C 3J7
    J Biol Chem 289:13186-96. 2014
    ..Here, we demonstrate that Hst3 instability in vivo is dependent upon the ubiquitin ligase SCF(Cdc4) and that Hst3 is phosphorylated at two Cdk1 sites, threonine 380 and threonine 384...
  25. ncbi Evaluation of a diffusion-driven mechanism for substrate ubiquitination by the SCF-Cdc34 ubiquitin ligase complex
    Matthew D Petroski
    Howard Hughes Medical Institute, Division of Biology, 156 29, California Institute of Technology, 1200 East California Boulevard, Pasadena, California 91125, USA
    Mol Cell 24:523-34. 2006
    ..We propose that interactions between Cdc34 approximately Ub and SCF directly activate ubiquitin transfer within a substrate-SCF-Cdc34 approximately Ub ternary complex...
  26. pmc Polyelectrostatic interactions of disordered ligands suggest a physical basis for ultrasensitivity
    Mikael Borg
    Department of Biochemistry, Faculty of Medicine, University of Toronto, Toronto, ON, Canada M5S 1A8
    Proc Natl Acad Sci U S A 104:9650-5. 2007
    ..of DNA replication in yeast requires elimination of the cyclin-dependent kinase inhibitor Sic1 via the SCF(Cdc4) ubiquitin ligase...
  27. pmc E2 enzyme inhibition by stabilization of a low-affinity interface with ubiquitin
    Hao Huang
    1 Centre for Systems Biology, Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Canada 2
    Nat Chem Biol 10:156-63. 2014
    ..Stabilization of the numerous other weak interactions between ubiquitin and UPS enzymes by small molecules may be a feasible strategy to selectively inhibit different UPS activities. ..
  28. pmc Dynamic ubiquitination of the mitogen-activated protein kinase kinase (MAPKK) Ste7 determines mitogen-activated protein kinase (MAPK) specificity
    Jillian H Hurst
    Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, North Carolina 27599 7260, USA
    J Biol Chem 288:18660-71. 2013
    ..Here, we show that the Skp1/Cullin/F-box ubiquitin ligase SCF(Cdc4) and the ubiquitin protease Ubp3 regulate Ste7 ubiquitination and signal specificity...
  29. pmc Sequential primed kinases create a damage-responsive phosphodegron on Eco1
    Nicholas A Lyons
    Department of Physiology, University of California, San Francisco, San Francisco, California, USA
    Nat Struct Mol Biol 20:194-201. 2013
    ..Eco1 activity falls after S phase due to Cdk1-dependent phosphorylation, which triggers ubiquitination by SCF(Cdc4)...
  30. pmc A dual E3 mechanism for Rub1 ligation to Cdc53
    Daniel C Scott
    Howard Hughes Medical Institute, St Jude Children s Research Hospital, Memphis, TN 38105, USA
    Mol Cell 39:784-96. 2010
    ..Our data reveal mechanisms by which two E3s function synergistically to promote UBL transfer from one E2 to a target...
  31. pmc Molecular basis for lysine specificity in the yeast ubiquitin-conjugating enzyme Cdc34
    Martin Sadowski
    Cell Cycle and Cancer Unit, St Vincent s Institute of Medical Research, 9 Princes St, Fitzroy, Melbourne, Victoria 3065, Australia
    Mol Cell Biol 30:2316-29. 2010
    ....
  32. pmc Signal-induced disassembly of the SCF ubiquitin ligase complex by Cdc48/p97
    James L Yen
    Department of Biological Chemistry, College of Medicine, University of California, Irvine, CA 92697 1700, USA
    Mol Cell 48:288-97. 2012
    ..Our results not only provide an additional layer of ubiquitin ligase regulation but also suggest that targeted, signal-dependent dissociation of multisubunit enzyme complexes is an important mechanism in control of enzyme function...
  33. pmc F-box protein specificity for g1 cyclins is dictated by subcellular localization
    Benjamin D Landry
    Program in Gene Function and Expression, University of Massachusetts Medical School, Worcester, MA, USA
    PLoS Genet 8:e1002851. 2012
    ..Here we show that two SCF ubiquitin ligases, SCF(Cdc4) and SCF(Grr1), redundantly target Cln3 for degradation...
  34. ncbi Role of predicted metalloprotease motif of Jab1/Csn5 in cleavage of Nedd8 from Cul1
    Gregory A Cope
    Department of Biology, California Institute of Technology Caltech, Pasadena, CA 91125, USA
    Science 298:608-11. 2002
    ..We propose that JAMM isopeptidases play important roles in a variety of physiological pathways...
  35. pmc Human CUL1 forms an evolutionarily conserved ubiquitin ligase complex (SCF) with SKP1 and an F-box protein
    S A Lyapina
    Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA
    Proc Natl Acad Sci U S A 95:7451-6. 1998
    ..SCF is composed of three proteins-ySKP1, CDC53 (Cullin), and the F-box protein CDC4-that are conserved from yeast to humans...
  36. ncbi High-level expression and purification of recombinant SCF ubiquitin ligases
    Ti Li
    Department of Pharmacology, University of Washington, Seattle, WA 98195, USA
    Methods Enzymol 398:125-42. 2005
    ..We propose that similar approaches can be used to obtain large quantities of other SCF and SCF-like complexes for biochemical and structural investigations...
  37. pmc Mutations in the hydrophobic core of ubiquitin differentially affect its recognition by receptor proteins
    Aydin Haririnia
    Department of Chemistry and Biochemistry, Center for Biomolecular Structure and Organization, University of Maryland, College Park, MD 20742, USA
    J Mol Biol 375:979-96. 2008
    ..These studies emphasize an unexpected role for Ub's core in molecular recognition and suggest that the diversity of protein-protein interactions in which Ub engages placed enormous constraints on its evolvability...
  38. pmc A refined two-hybrid system reveals that SCF(Cdc4)-dependent degradation of Swi5 contributes to the regulatory mechanism of S-phase entry
    Tsutomu Kishi
    Kishi Initiative Research Unit, RIKEN, 2 1 Hirosawa, Wako, Saitama 351 0198, Japan
    Proc Natl Acad Sci U S A 105:14497-502. 2008
    Ubiquitin-dependent degradation is implicated in various cellular regulatory mechanisms. The SCF(Cdc4) (Skp1, Cullin/Cdc53, and the F-box protein Cdc4) complex is an ubiquitin ligase complex that acts as a regulator of cell cycle, signal ..
  39. 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...
  40. pmc Sir2 histone deacetylase prevents programmed cell death caused by sustained activation of the Hog1 stress-activated protein kinase
    Alexandre Vendrell
    Cell Signaling Unit, Departament de Ciencies Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona E 08003, Valencia, Spain
    EMBO Rep 12:1062-8. 2011
    ..Mutations of the SCF(CDC4) ubiquitin ligase complex suppress cell death by preventing the degradation of Msn2 and Msn4 transcription factors...
  41. ncbi Interactome and interface protocol (2IP): a novel strategy for high sensitivity topology mapping of protein complexes
    Rasanjala Weerasekera
    Centre for Research in Neurodegenerative Diseases, University of Toronto, Ontario, Canada
    Proteomics 7:3835-52. 2007
    ..This protocol requires low picomole sample quantities, can be applied to multisubunit protein complexes, and does not rely on specialized data mining software...
  42. pmc B-cyclin/CDKs regulate mitotic spindle assembly by phosphorylating kinesins-5 in budding yeast
    Mark K Chee
    Department of Biology, Duke University, Durham, North Carolina, United States of America
    PLoS Genet 6:e1000935. 2010
    ..previously been shown in a variety of model systems that B-type cyclin/CDK complexes, kinesin-5 motors, and the SCF(Cdc4) ubiquitin ligase are required for the separation of spindle poles and assembly of a bipolar spindle...
  43. pmc Dynamic equilibrium engagement of a polyvalent ligand with a single-site receptor
    Tanja Mittag
    Program in Molecular Structure and Function, Hospital for Sick Children, 555 University Avenue, Toronto, ON, Canada M5G 1X8
    Proc Natl Acad Sci U S A 105:17772-7. 2008
    ..The disordered cyclin-dependent kinase (CDK) inhibitor Sic1 interacts with a single site on its receptor Cdc4 only upon phosphorylation of its multiple dispersed CDK sites...
  44. pmc Domain architecture of the regulators of calcineurin (RCANs) and identification of a divergent RCAN in yeast
    Sohum Mehta
    Department of Biology, Johns Hopkins University, 3400 N Charles Street, Baltimore, MD 21218, USA
    Mol Cell Biol 29:2777-93. 2009
    ..other highly conserved motifs plus the GSK-3 phosphorylation site in RCANs, along with the E3 ubiquitin ligase SCF(Cdc4), were required for stimulation of calcineurin signaling in yeast...
  45. doi Factors affecting the diversity of DNA replication licensing control in eukaryotes
    Lucy S Drury
    Cancer Research UK London Research Institute, Clare Hall Laboratories, South Mimms, Herts EN6 3LD, UK
    Curr Biol 19:530-5. 2009
    ..These experiments provide a framework for understanding the diversity of licensing regulation in eukaryotes and provide new tools for manipulating the chromosome-replication cycle...
  46. pmc A longevity protein, Lag2, interacts with SCF complex and regulates SCF function
    Yuan Liu
    Division of Biological Science, Graduate School of Science, Nagoya University, Chikusa ku, Nagoya, Aichi, Japan
    EMBO J 28:3366-77. 2009
    ..These observations thus indicate that Lag2 has a significant function in regulating the SCF complex by controlling its ubiquitin ligase activities and its rubylation cycle...
  47. pmc Synthetic lethal genetic interactions that decrease somatic cell proliferation in Caenorhabditis elegans identify the alternative RFC CTF18 as a candidate cancer drug target
    Jessica McLellan
    Department of Medical Genetics, The University of British Columbia, Vancouver, BC, Canada
    Mol Biol Cell 20:5306-13. 2009
    ..elegans. Furthermore, the C. elegans assay system will contribute to our knowledge of genetic interactions in a multicellular animal and is a powerful approach to identify new cancer therapeutic targets...
  48. pmc Chemical genetics screen for enhancers of rapamycin identifies a specific inhibitor of an SCF family E3 ubiquitin ligase
    Mariam Aghajan
    Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, and the Molecular Biology Institute, University of California, Los Angeles, California, USA
    Nat Biotechnol 28:738-42. 2010
    ..We show here that SMER3 inhibits SCF(Met30) in vivo and in vitro, but not the closely related SCF(Cdc4)...
  49. doi Remodeling of the SCF complex-mediated ubiquitination system by compositional alteration of incorporated F-box proteins
    Mitsunori Kato
    Department of Computational Biology, Graduate School of Frontier Sciences, University of Tokyo, Kashiwa, Japan
    Proteomics 10:115-23. 2010
    ..Compositional alteration of incorporated F-box proteins may redirect the activity of this system toward appropriate substrates to be ubiquitinated under individual conditions for the maintenance of cellular homeostasis...
  50. pmc An allosteric inhibitor of substrate recognition by the SCF(Cdc4) ubiquitin ligase
    Stephen Orlicky
    Center for Systems Biology, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Canada
    Nat Biotechnol 28:733-7. 2010
    ..dicarboxylic acid compound, called SCF-I2, as an inhibitor of substrate recognition by the yeast F-box protein Cdc4 using a fluorescence polarization screen to monitor the displacement of a fluorescein-labeled phosphodegron peptide...
  51. pmc Systematic analysis of essential genes reveals important regulators of G protein signaling
    Steven D Cappell
    Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
    Mol Cell 38:746-57. 2010
    ..Further genetic and biochemical analysis reveals that SCF(Cdc4) acts together with the Cdc34 ubiquitin-conjugating enzyme at the level of the G protein; promotes degradation of ..
  52. pmc Structure/function implications in a dynamic complex of the intrinsically disordered Sic1 with the Cdc4 subunit of an SCF ubiquitin ligase
    Tanja Mittag
    Program in Molecular Structure and Function, The Hospital for Sick Children, 555 University Avenue, Toronto, ON M5G 1X8, Canada
    Structure 18:494-506. 2010
    ..One such dynamic complex involves the intrinsically disordered Sic1 with its partner Cdc4 in regulation of yeast cell cycle progression...
  53. pmc Glucose and ras activity influence the ubiquitin ligases APC/C and SCF in Saccharomyces cerevisiae
    S Irniger
    Institute of Microbiology and Genetics, Georg August University, D 37077 Gottingen, Germany
    Genetics 154:1509-21. 2000
    ..We conclude that glucose and Ras proteins influence the APC/C and the SCF complex in an opposite manner. These ubiquitin ligases might represent novel targets for modulating cell division in response to growth conditions...
  54. ncbi SCM4, a gene that suppresses mutant cdc4 function in budding yeast
    S A Smith
    Department of Biochemistry and Molecular Biology, University of Manchester, UK
    Mol Gen Genet 235:285-91. 1992
    The gene SCM4 encodes a protein which suppresses a temperature-sensitive allele of the cell division cycle gene CDC4 in Saccharomyces cerevisiae. SCM4 was cloned on a 1...
  55. ncbi The CDC4 gene product is associated with the yeast nuclear skeleton
    W J Choi
    Department of Molecular Biology, University of Southern California, Los Angeles
    Biochem Biophys Res Commun 172:1324-30. 1990
    The CDC4 gene product of Saccharomyces cerevisiae is required at the late G1/S phase boundary of the cell cycle. In an attempt to better understand the function of CDC4, we performed experiments to localize this protein in the yeast cell...
  56. pmc Characterization of G1 checkpoint control in the yeast Saccharomyces cerevisiae following exposure to DNA-damaging agents
    W Siede
    Department of Pathology, University of Texas Southwestern Medical Center, Dallas 75235
    Genetics 138:271-81. 1994
    ..one at START (a G1 checkpoint characterized by pheromone sensitivity of arrested cells) and one between the CDC4- and CDC7-mediated steps (termed the G1/S checkpoint)...
  57. ncbi G2/M checkpoint genes of Saccharomyces cerevisiae: further evidence for roles in DNA replication and/or repair
    D Lydall
    Department of Molecular and Cellular Biology, University of Arizona, Tucson 85721, USA
    Mol Gen Genet 256:638-51. 1997
    ..Rfc1p (cdc44), DNA pol alpha (cdc17) and DNA pol delta (cdc2) but has much weaker effects on cdc6, cdc9, cdc15 and CDC4 strains...
  58. 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
    ..CDC34 activity fail to degrade Sic1p and fail to enter S-phase, a phenotype that is also shared with cells lacking CDC4 and CDC53 activity. Here we demonstrate that Cdc4p, Cdc34p, and Cdc53p interact in vivo...
  59. pmc Cdc53 is a scaffold protein for multiple Cdc34/Skp1/F-box proteincomplexes that regulate cell division and methionine biosynthesis in yeast
    E E Patton
    Programme in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Canada M5G 1X5
    Genes Dev 12:692-705. 1998
    ..enzyme Cdc34 in conjunction with an E3 ubiquitin ligase complex composed of Skp1, Cdc53 and the F-box protein, Cdc4 (the SCFCdc4 complex)...
  60. pmc Modification of yeast Cdc53p by the ubiquitin-related protein rub1p affects function of the SCFCdc4 complex
    D Lammer
    Biology Department, Indiana University, Bloomington, Indiana, 47405 USA
    Genes Dev 12:914-26. 1998
    ..A deletion allele of ENR2 is lethal with temperature-sensitive alleles of cdc34 and enhances the phenotypes of cdc4, cdc53, and skp1, strongly implying that Rub1p conjugation to Cdc53p is required for optimal assembly or function ..
  61. pmc Association of RPA with chromosomal replication origins requires an Mcm protein, and is regulated by Rad53, and cyclin- and Dbf4-dependent kinases
    T Tanaka
    Research Institute of Molecular Pathology, A 1030 Vienna, Austria
    EMBO J 17:5182-91. 1998
    ..Thus, in the presence of active S-CDKs and Dbf4/Cdc7, Mcms may open origins and thereby facilitate the loading of RPA...
  62. ncbi The Cdc6 protein is ubiquitinated in vivo for proteolysis in Saccharomyces cerevisiae
    M Sanchez
    Instituto de Microbiología Bioquímica Centro de Investigación del Cáncer, Departamento de Microbiologia y Genetica, Edificio Departamental, Campus Miguel de Unamuno, CSIC Universidad de Salamanca, 37007 Salamanca, Spain
    J Biol Chem 274:9092-7. 1999
    ..We report here that the Cdc6p protein is degraded in a Cdc4-dependent manner, suggesting that phosphorylated Cdc6 is specifically recognized by the ubiquitin-mediated ..
  63. ncbi Rbx1, a component of the VHL tumor suppressor complex and SCF ubiquitin ligase
    T Kamura
    Howard Hughes Medical Institute, Program in Molecular and Cell Biology, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA
    Science 284:657-61. 1999
    ..These findings provide a further link between VHL and the cellular ubiquitination machinery...
  64. ncbi SGT1 encodes an essential component of the yeast kinetochore assembly pathway and a novel subunit of the SCF ubiquitin ligase complex
    K Kitagawa
    Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, Canada
    Mol Cell 4:21-33. 1999
    ..sgt1-5 (G1 allele) mutants are defective in Sic1p turnover in vivo and Cln1p ubiquitination in vitro. Human SGT1 rescues an sgt1 null mutation, suggesting that the function of SGT1 is conserved in evolution...
  65. 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...
  66. 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
    ..Here, we review the substrates and pathways regulated by the yeast F-box proteins Cdc4, Grr1 and Met30...
  67. pmc Degradation of the transcription factor Gcn4 requires the kinase Pho85 and the SCF(CDC4) ubiquitin-ligase complex
    A Meimoun
    Department of Microbiology, Technion B Rappaport Faculty of Medicine, Haifa 31096, Israel
    Mol Biol Cell 11:915-27. 2000
    ..Here we report that SCF(CDC4), a recently characterized protein complex that acts in conjunction with the ubiquitin-conjugating enzyme Cdc34 to ..
  68. pmc Phosphorylation of the Sic1 inhibitor of B-type cyclins in Saccharomyces cerevisiae is not essential but contributes to cell cycle robustness
    Frederick R Cross
    The Rockefeller University, New York, New York 10021, USA
    Genetics 176:1541-55. 2007
    ....
  69. pmc Isolation and characterization of HRT1 using a genetic screen for mutants unable to degrade Gic2p in saccharomyces cerevisiae
    M Blondel
    Swiss Institute for Experimental Cancer Research ISREC, 1066 Epalinges VD, Switzerland
    Genetics 155:1033-44. 2000
    ..Taken together, these results suggest that Hrt1p is a core subunit of multiple SCF complexes...
  70. pmc Identification of Cdc6 protein domains involved in interaction with Mcm2 protein and Cdc4 protein in budding yeast cells
    S W Jang
    Graduate School of Biotechnology, Department of Genetic Engineering, Kyung Hee University, Yongin, Kyonggi Do, 449 701, Korea
    Biochem J 354:655-61. 2001
    ....
  71. pmc Separate SCF(CDC4) recognition elements target Cdc6 for proteolysis in S phase and mitosis
    G Perkins
    ICRF Clare Hall Laboratories, South Mimms EN6 3LD, UK
    EMBO J 20:4836-45. 2001
    ..DNA replication initiation factor is targeted for ubiquitin-mediated proteolysis by the E3 ubiquitin ligase SCF(CDC4) from the end of G1phase until mitosis in the budding yeast Saccharomyces cerevisiae...
  72. ncbi Cdc4 is involved in the transcriptional control of OCH1, a gene encoding alpha-1,6-mannosyltransferase in Saccharomyces cerevisiae
    Zhifeng Cui
    Institute of Molecular and Cell Biology, National Institute of Advanced Industrial Science and Technology, Tsukuba Central 6, 1 1 Higashi, Tsukuba, Ibaraki 305 8566, Japan
    Yeast 19:69-77. 2002
    ..bon1-1 is an allele of CDC4 (cdc4(bon)) and leads to the additional phenotypes of temperature sensitivity and abnormal cell morphology...
  73. ncbi Structural basis for phosphodependent substrate selection and orientation by the SCFCdc4 ubiquitin ligase
    Stephen Orlicky
    Program in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, M5G 1X5, Toronto, Ontario, Canada
    Cell 112:243-56. 2003
    ..the SCFCdc4 ubiquitin ligase at the onset of S phase requires phosphorylation of Sic1 on at least six of its nine Cdc4-phosphodegron (CPD) sites. A 2...
  74. pmc Overproduction of polypeptides corresponding to the amino terminus of the F-box proteins Cdc4p and Met30p inhibits ubiquitin ligase activities of their SCF complexes
    Cheryl Dixon
    Department of Biochemistry and Molecular Biology, Louisiana State University Health Science Center, Shreveport, Louisiana 71130 3932, USA
    Eukaryot Cell 2:123-33. 2003
    ..These results suggest a common means to inhibit specific SCF complexes in vivo...
  75. ncbi Context of multiubiquitin chain attachment influences the rate of Sic1 degradation
    Matthew D Petroski
    Howard Hughes Medical Institute, Division of Biology 156 29, California Institute of Technology, 1200 E California Boulevard, Pasadena, CA 91125, USA
    Mol Cell 11:1435-44. 2003
    ..Moreover, although K0N can be ubiquitinated by SCF(Cdc4)/Cdc34 in vitro in the absence (but not in the presence) of S-CDK, it is degraded slowly...
  76. ncbi Functional interaction of 13 yeast SCF complexes with a set of yeast E2 enzymes in vitro
    Bart M Kus
    Banting and Best Department of Medical Research, University of Toronto, Ontario
    Proteins 54:455-67. 2004
    ..We have found that the ubiquitination of Sic1 by the reconstituted SCF(Cdc4) complex was specifically catalyzed by two of the five E2 enzymes tested in vitro; Cdc34 and Ubc4...
  77. ncbi Phosphorylation-dependent binding of mitotic cyclins to Cdc6 contributes to DNA replication control
    Satoru Mimura
    Cancer Research UK London Research Institute, Clare Hall Laboratories, Blanche Lane, South Mimms, Potters Bar, Herts EN6 3LD, UK
    Nature 431:1118-23. 2004
    ..We propose that direct binding of cyclins to phosphopeptide motifs may be a widespread phenomenon contributing to the targeting of CDKs to substrates...
  78. 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
    ..T273 in a predicted high-affinity Cdc4 binding motif is phosphorylated by Fus3 both in vitro and in vivo...
  79. pmc Effects of the mitotic cell-cycle mutation cdc4 on yeast meiosis
    G Simchen
    Genetics 86:57-72. 1977
    The mitotic cell-cycle mutation cdc4 has been reported to block the initiation of nuclear DNA replication and the separation of spindle plaques after their replication...
  80. ncbi ATP hydrolysis-dependent disassembly of the 26S proteasome is part of the catalytic cycle
    Shalon E Babbitt
    Edward A Doisy Department of Biochemistry and Molecular Biology, St Louis University School of Medicine, St Louis, MO 63104, USA
    Cell 121:553-65. 2005
    ..This is the first demonstration that a controlled dissociation of the 19S regulatory particles from the 26S proteasome is part of the mechanism of protein degradation...
  81. 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
    ..box motif responsible for the anaphase promoting complex-mediated destruction of Clb5 but contains putative Cdc4 degron motifs in the N terminus...
  82. pmc The novel F-box protein Mfb1p regulates mitochondrial connectivity and exhibits asymmetric localization in yeast
    Noriko Kondo-Okamoto
    Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT 84112, USA
    Mol Biol Cell 17:3756-67. 2006
    ..We propose that Mfb1p operates in a novel pathway regulating mitochondrial tubular connectivity...

Research Grants1

  1. How do cyclins drive the cell cycle?
    Frederick R Cross; Fiscal Year: 2010
    ..Overall, we are interested in regulation of cell cycle dynamics, and in cyclin-specific pathways promoting individual cell cycle events. ..