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

Top Publications

  1. Nash P, Tang X, Orlicky S, Chen Q, Gertler F, Mendenhall M, et al. Multisite phosphorylation of a CDK inhibitor sets a threshold for the onset of DNA replication. Nature. 2001;414:514-21 pubmed
    ..The F-box protein Cdc4 captures phosphorylated forms of the cyclin-dependent kinase inhibitor Sic1 for ubiquitination in late G1 phase, an ..
  2. Goh P, Surana U. Cdc4, a protein required for the onset of S phase, serves an essential function during G(2)/M transition in Saccharomyces cerevisiae. Mol Cell Biol. 1999;19:5512-22 pubmed
    Saccharomyces cerevisiae proteins Cdc4 and Cdc20 contain WD40 repeats and participate in proteolytic processes...
  3. Seol J, Feldman R, Zachariae W, Correll C, Lyapina S, Chi Y, et al. Cdc53/cullin and the essential Hrt1 RING-H2 subunit of SCF define a ubiquitin ligase module that activates the E2 enzyme Cdc34. Genes Dev. 1999;13:1614-26 pubmed
    ..Hrt1 assembles into recombinant SCF complexes and individually binds Cdc4, Cdc53 and Cdc34, but not Skp1...
  4. Skowyra D, Koepp D, Kamura T, Conrad M, Conaway R, Conaway J, et al. Reconstitution of G1 cyclin ubiquitination with complexes containing SCFGrr1 and Rbx1. Science. 1999;284:662-5 pubmed
    ..Rbx1, which is also a component of the von Hippel-Lindau tumor suppressor complex, may define a previously unrecognized class of E3-associated proteins. ..
  5. Verma R, Feldman R, Deshaies R. SIC1 is ubiquitinated in vitro by a pathway that requires CDC4, CDC34, and cyclin/CDK activities. Mol Biol Cell. 1997;8:1427-37 pubmed
    ..Genetic data suggest that SIC1 proteolysis is mediated by the ubiquitin pathway and requires the action of CDC34, CDC4, CDC53, SKP1, and CLN/CDC28...
  6. Tang X, Orlicky S, Mittag T, Csizmok V, Pawson T, Forman Kay J, et al. Composite low affinity interactions dictate recognition of the cyclin-dependent kinase inhibitor Sic1 by the SCFCdc4 ubiquitin ligase. Proc Natl Acad Sci U S A. 2012;109:3287-92 pubmed publisher
    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...
  7. Schwob E, Bohm T, Mendenhall M, Nasmyth K. The B-type cyclin kinase inhibitor p40SIC1 controls the G1 to S transition in S. cerevisiae. Cell. 1994;79:233-44 pubmed
    ..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. ..
  8. Mathias N, Johnson S, Winey M, Adams A, Goetsch L, Pringle J, et al. Cdc53p acts in concert with Cdc4p and Cdc34p to control the G1-to-S-phase transition and identifies a conserved family of proteins. Mol Cell Biol. 1996;16:6634-43 pubmed
    ..During G1, CDC4, encoding a WD-40 repeat protein, and CDC34, encoding a ubiquitin-conjugating enzyme, are involved in the ..
  9. Tang X, Orlicky S, Lin Z, Willems A, Neculai D, Ceccarelli D, et al. Suprafacial orientation of the SCFCdc4 dimer accommodates multiple geometries for substrate ubiquitination. Cell. 2007;129:1165-76 pubmed
    ..WD40 repeat F box proteins, such as Cdc4 and beta-TrCP, contain a conserved dimerization motif called the D domain...

More Information


  1. Bao M, Shock T, Madhani H. 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. Eukaryot Cell. 2010;9:31-6 pubmed publisher
    ..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...
  2. Blondel M, Galan J, Chi Y, LaFourcade C, Longaretti C, Deshaies R, et al. Nuclear-specific degradation of Far1 is controlled by the localization of the F-box protein Cdc4. EMBO J. 2000;19:6085-97 pubmed
    ..Here we show that SCF(Cdc4) ubiquitylates Far1 in the nucleus, which in turn targets the multi-ubiquitylated protein to 26S proteasomes most ..
  3. Skowyra D, Craig K, Tyers M, Elledge S, Harper J. F-box proteins are receptors that recruit phosphorylated substrates to the SCF ubiquitin-ligase complex. Cell. 1997;91:209-19 pubmed
    ..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 ..
  4. Pal B, Chan N, Helfenbaum L, Tan K, Tansey W, Gething M. SCFCdc4-mediated degradation of the Hac1p transcription factor regulates the unfolded protein response in Saccharomyces cerevisiae. Mol Biol Cell. 2007;18:426-40 pubmed
    ..that degradation of Hac1p by the proteasome involves the E2 ubiquitin-conjugating enzyme Ubc3/Cdc34p and the SCF(Cdc4) E3 complex...
  5. Tang X, Orlicky S, Liu Q, Willems A, Sicheri F, Tyers M. Genome-wide surveys for phosphorylation-dependent substrates of SCF ubiquitin ligases. Methods Enzymol. 2005;399:433-58 pubmed
    ..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 ..
  6. Kishi T, Ikeda A, Nagao R, Koyama N. The SCFCdc4 ubiquitin ligase regulates calcineurin signaling through degradation of phosphorylated Rcn1, an inhibitor of calcineurin. Proc Natl Acad Sci U S A. 2007;104:17418-23 pubmed
    ..Here we show that phosphorylation of yeast RCN, Rcn1, triggers degradation through the SCF(Cdc4) ubiquitin ligase complex...
  7. Bai C, Sen P, Hofmann K, Ma L, Goebl M, Harper J, et al. SKP1 connects cell cycle regulators to the ubiquitin proteolysis machinery through a novel motif, the F-box. Cell. 1996;86:263-74 pubmed
    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...
  8. Feldman R, Correll C, Kaplan K, Deshaies R. A complex of Cdc4p, Skp1p, and Cdc53p/cullin catalyzes ubiquitination of the phosphorylated CDK inhibitor Sic1p. Cell. 1997;91:221-30 pubmed
    ..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. ..
  9. Drury L, Perkins G, Diffley J. The Cdc4/34/53 pathway targets Cdc6p for proteolysis in budding yeast. EMBO J. 1997;16:5966-76 pubmed
    ..Likewise, mutations in the Cdc4/34/53 pathway involved in ubiquitin-mediated degradation block proteolysis and genetic evidence is presented ..
  10. Knapp D, Bhoite L, Stillman D, Nasmyth K. The transcription factor Swi5 regulates expression of the cyclin kinase inhibitor p40SIC1. Mol Cell Biol. 1996;16:5701-7 pubmed
    ..inhibitor p40SIC1 in late G1, which is mediated by the ubiquitin-conjugating enzyme Cdc34 and two other proteins, Cdc4 and Cdc53...
  11. Liu Q, Larsen B, Ricicova M, Orlicky S, Tekotte H, Tang X, et al. SCFCdc4 enables mating type switching in yeast by cyclin-dependent kinase-mediated elimination of the Ash1 transcriptional repressor. Mol Cell Biol. 2011;31:584-98 pubmed publisher
    ..Here, we report that the ubiquitin ligase SCF(Cdc4) mediates the phosphorylation-dependent elimination of Ash1...
  12. Hao B, Oehlmann S, Sowa M, Harper J, Pavletich N. Structure of a Fbw7-Skp1-cyclin E complex: multisite-phosphorylated substrate recognition by SCF ubiquitin ligases. Mol Cell. 2007;26:131-43 pubmed
    ..Biochemical data indicate that the closely related yeast SCF(Cdc4) complex recognizes the multisite phosphorylated Sic1 substrate similarly and identify three doubly phosphorylated ..
  13. Kamura T, Koepp D, Conrad M, Skowyra D, Moreland R, Iliopoulos O, et al. Rbx1, a component of the VHL tumor suppressor complex and SCF ubiquitin ligase. Science. 1999;284:657-61 pubmed
    ..These findings provide a further link between VHL and the cellular ubiquitination machinery. ..
  14. Edenberg E, Vashisht A, Topacio B, Wohlschlegel J, Toczyski D. Hst3 is turned over by a replication stress-responsive SCF(Cdc4) phospho-degron. Proc Natl Acad Sci U S A. 2014;111:5962-7 pubmed publisher
    ..Here, we show that Hst3 is targeted for turnover by the ubiquitin ligase SCF(Cdc4) after phosphorylation of a multisite degron...
  15. Weerasekera R, She Y, Markham K, Bai Y, Opalka N, Orlicky S, et al. Interactome and interface protocol (2IP): a novel strategy for high sensitivity topology mapping of protein complexes. Proteomics. 2007;7:3835-52 pubmed
    ..This protocol requires low picomole sample quantities, can be applied to multisubunit protein complexes, and does not rely on specialized data mining software. ..
  16. Delgoshaie N, Tang X, Kanshin E, Williams E, Rudner A, Thibault P, et al. Regulation of the histone deacetylase Hst3 by cyclin-dependent kinases and the ubiquitin ligase SCFCdc4. J Biol Chem. 2014;289:13186-96 pubmed publisher
    ..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...
  17. Petroski M, Deshaies R. Context of multiubiquitin chain attachment influences the rate of Sic1 degradation. Mol Cell. 2003;11:1435-44 pubmed
    ..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...
  18. Mimura S, Seki T, Tanaka S, Diffley J. Phosphorylation-dependent binding of mitotic cyclins to Cdc6 contributes to DNA replication control. Nature. 2004;431:1118-23 pubmed
    ..We propose that direct binding of cyclins to phosphopeptide motifs may be a widespread phenomenon contributing to the targeting of CDKs to substrates. ..
  19. Lammer D, Mathias N, Laplaza J, Jiang W, Liu Y, Callis J, et al. Modification of yeast Cdc53p by the ubiquitin-related protein rub1p affects function of the SCFCdc4 complex. Genes Dev. 1998;12:914-26 pubmed
    ..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 ..
  20. Cope G, Suh G, Aravind L, Schwarz S, Zipursky S, Koonin E, et al. Role of predicted metalloprotease motif of Jab1/Csn5 in cleavage of Nedd8 from Cul1. Science. 2002;298:608-11 pubmed
    ..We propose that JAMM isopeptidases play important roles in a variety of physiological pathways. ..
  21. Zhou P, Howley P. Ubiquitination and degradation of the substrate recognition subunits of SCF ubiquitin-protein ligases. Mol Cell. 1998;2:571-80 pubmed
    ..The finding that the F box-containing SCF components are unstable suggests a mechanism of regulating SCF function through ubiquitination and proteolysis of F box components. ..
  22. Cross F, Schroeder L, Bean J. Phosphorylation of the Sic1 inhibitor of B-type cyclins in Saccharomyces cerevisiae is not essential but contributes to cell cycle robustness. Genetics. 2007;176:1541-55 pubmed
  23. Jager S, Strayle J, Heinemeyer W, Wolf D. Cic1, an adaptor protein specifically linking the 26S proteasome to its substrate, the SCF component Cdc4. EMBO J. 2001;20:4423-31 pubmed
    ..Whereas degradation of short-lived test proteins is not affected, cic1 mutants stabilize the F-box proteins Cdc4 and Grr1, substrate recognition subunits of the SCF complex...
  24. Blondel M, Galan J, Peter M. Isolation and characterization of HRT1 using a genetic screen for mutants unable to degrade Gic2p in saccharomyces cerevisiae. Genetics. 2000;155:1033-44 pubmed
    ..Taken together, these results suggest that Hrt1p is a core subunit of multiple SCF complexes. ..
  25. Orlicky S, Tang X, Neduva V, Elowe N, Brown E, Sicheri F, et al. An allosteric inhibitor of substrate recognition by the SCF(Cdc4) ubiquitin ligase. Nat Biotechnol. 2010;28:733-7 pubmed publisher
    ..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...
  26. Borg M, Mittag T, Pawson T, Tyers M, Forman Kay J, Chan H. Polyelectrostatic interactions of disordered ligands suggest a physical basis for ultrasensitivity. Proc Natl Acad Sci U S A. 2007;104:9650-5 pubmed
    ..of DNA replication in yeast requires elimination of the cyclin-dependent kinase inhibitor Sic1 via the SCF(Cdc4) ubiquitin ligase...
  27. Cappell S, Baker R, Skowyra D, Dohlman H. Systematic analysis of essential genes reveals important regulators of G protein signaling. Mol Cell. 2010;38:746-57 pubmed publisher
    ..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 ..
  28. Huang H, Ceccarelli D, Orlicky S, St Cyr D, Ziemba A, Garg P, et al. E2 enzyme inhibition by stabilization of a low-affinity interface with ubiquitin. Nat Chem Biol. 2014;10:156-163 pubmed publisher
    ..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. ..
  29. Kitagawa K, Skowyra D, Elledge S, Harper J, Hieter P. SGT1 encodes an essential component of the yeast kinetochore assembly pathway and a novel subunit of the SCF ubiquitin ligase complex. Mol Cell. 1999;4:21-33 pubmed
    ..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. ..
  30. Kus B, Caldon C, Andorn Broza R, Edwards A. Functional interaction of 13 yeast SCF complexes with a set of yeast E2 enzymes in vitro. Proteins. 2004;54:455-67 pubmed
    ..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...
  31. Scott D, Monda J, Grace C, Duda D, Kriwacki R, Kurz T, et al. A dual E3 mechanism for Rub1 ligation to Cdc53. Mol Cell. 2010;39:784-96 pubmed publisher
    ..Our data reveal mechanisms by which two E3s function synergistically to promote UBL transfer from one E2 to a target. ..
  32. Lydall D, Weinert T. G2/M checkpoint genes of Saccharomyces cerevisiae: further evidence for roles in DNA replication and/or repair. Mol Gen Genet. 1997;256:638-51 pubmed
    ..Rfc1p (cdc44), DNA pol alpha (cdc17) and DNA pol delta (cdc2) but has much weaker effects on cdc6, cdc9, cdc15 and CDC4 strains...
  33. Sadowski M, Suryadinata R, Lai X, Heierhorst J, Sarcevic B. Molecular basis for lysine specificity in the yeast ubiquitin-conjugating enzyme Cdc34. Mol Cell Biol. 2010;30:2316-29 pubmed publisher
  34. Meimoun A, Holtzman T, Weissman Z, McBride H, Stillman D, Fink G, et al. Degradation of the transcription factor Gcn4 requires the kinase Pho85 and the SCF(CDC4) ubiquitin-ligase complex. Mol Biol Cell. 2000;11:915-27 pubmed
    ..Here we report that SCF(CDC4), a recently characterized protein complex that acts in conjunction with the ubiquitin-conjugating enzyme Cdc34 to ..
  35. Irniger S, Baumer M, Braus G. Glucose and ras activity influence the ubiquitin ligases APC/C and SCF in Saccharomyces cerevisiae. Genetics. 2000;154:1509-21 pubmed
    ..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. ..
  36. Tanaka T, Nasmyth K. Association of RPA with chromosomal replication origins requires an Mcm protein, and is regulated by Rad53, and cyclin- and Dbf4-dependent kinases. EMBO J. 1998;17:5182-91 pubmed
    ..Thus, in the presence of active S-CDKs and Dbf4/Cdc7, Mcms may open origins and thereby facilitate the loading of RPA. ..
  37. Chee M, Haase S. B-cyclin/CDKs regulate mitotic spindle assembly by phosphorylating kinesins-5 in budding yeast. PLoS Genet. 2010;6:e1000935 pubmed publisher
    ..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...
  38. Barbey R, Baudouin Cornu P, Lee T, Rouillon A, Zarzov P, Tyers M, et al. Inducible dissociation of SCF(Met30) ubiquitin ligase mediates a rapid transcriptional response to cadmium. EMBO J. 2005;24:521-32 pubmed
    ..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. ..
  39. Aghajan M, Jonai N, Flick K, Fu F, Luo M, Cai X, et al. Chemical genetics screen for enhancers of rapamycin identifies a specific inhibitor of an SCF family E3 ubiquitin ligase. Nat Biotechnol. 2010;28:738-42 pubmed publisher
    ..We show here that SMER3 inhibits SCF(Met30) in vivo and in vitro, but not the closely related SCF(Cdc4)...
  40. Hurst J, Dohlman H. Dynamic ubiquitination of the mitogen-activated protein kinase kinase (MAPKK) Ste7 determines mitogen-activated protein kinase (MAPK) specificity. J Biol Chem. 2013;288:18660-71 pubmed publisher
    ..Here, we show that the Skp1/Cullin/F-box ubiquitin ligase SCF(Cdc4) and the ubiquitin protease Ubp3 regulate Ste7 ubiquitination and signal specificity...
  41. Kishi T, Ikeda A, Koyama N, Fukada J, Nagao R. A refined two-hybrid system reveals that SCF(Cdc4)-dependent degradation of Swi5 contributes to the regulatory mechanism of S-phase entry. Proc Natl Acad Sci U S A. 2008;105:14497-502 pubmed publisher
    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 ..
  42. Mehta S, Li H, Hogan P, Cunningham K. Domain architecture of the regulators of calcineurin (RCANs) and identification of a divergent RCAN in yeast. Mol Cell Biol. 2009;29:2777-93 pubmed publisher
    ..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...
  43. Landry B, Doyle J, Toczyski D, Benanti J. F-box protein specificity for g1 cyclins is dictated by subcellular localization. PLoS Genet. 2012;8:e1002851 pubmed publisher
    ..Here we show that two SCF ubiquitin ligases, SCF(Cdc4) and SCF(Grr1), redundantly target Cln3 for degradation...
  44. Perkins G, Drury L, Diffley J. Separate SCF(CDC4) recognition elements target Cdc6 for proteolysis in S phase and mitosis. EMBO J. 2001;20:4836-45 pubmed
    ..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...
  45. Jang S, Elsasser S, Campbell J, Kim J. Identification of Cdc6 protein domains involved in interaction with Mcm2 protein and Cdc4 protein in budding yeast cells. Biochem J. 2001;354:655-61 pubmed
  46. Kato M, Kito K, Ota K, Ito T. Remodeling of the SCF complex-mediated ubiquitination system by compositional alteration of incorporated F-box proteins. Proteomics. 2010;10:115-23 pubmed publisher
    ..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. ..
  47. Smith S, Kumar P, Johnston I, Rosamond J. SCM4, a gene that suppresses mutant cdc4 function in budding yeast. Mol Gen Genet. 1992;235:285-91 pubmed
    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...
  48. Haririnia A, Verma R, Purohit N, Twarog M, Deshaies R, Bolon D, et al. Mutations in the hydrophobic core of ubiquitin differentially affect its recognition by receptor proteins. J Mol Biol. 2008;375:979-96 pubmed
    ..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. ..
  49. Deffenbaugh A, Scaglione K, Zhang L, Moore J, Buranda T, Sklar L, et al. Release of ubiquitin-charged Cdc34-S - Ub from the RING domain is essential for ubiquitination of the SCF(Cdc4)-bound substrate Sic1. Cell. 2003;114:611-22 pubmed
    The S. cerevisiae SCF(Cdc4) is a prototype of RING-type SCF E3s, which recruit substrates for polyubiquitination by the Cdc34 ubiquitin-conjugating enzyme...
  50. Scaglione K, Bansal P, Deffenbaugh A, Kiss A, Moore J, Korolev S, et al. SCF E3-mediated autoubiquitination negatively regulates activity of Cdc34 E2 but plays a nonessential role in the catalytic cycle in vitro and in vivo. Mol Cell Biol. 2007;27:5860-70 pubmed 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) ..
  51. Simchen G, Hirschberg J. Effects of the mitotic cell-cycle mutation cdc4 on yeast meiosis. Genetics. 1977;86:57-72 pubmed
    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...
  52. Sedgwick C, Rawluk M, Decesare J, Raithatha S, Wohlschlegel J, Semchuk P, et al. Saccharomyces cerevisiae Ime2 phosphorylates Sic1 at multiple PXS/T sites but is insufficient to trigger Sic1 degradation. Biochem J. 2006;399:151-60 pubmed
    ..In proliferating cells Cln-Cdc28 complexes phosphorylate Sic1, which stimulates binding of Sic1 to SCF(Cdc4) and triggers its proteosome mediated destruction...
  53. Willems A, Goh T, Taylor L, Chernushevich I, Shevchenko A, Tyers M. SCF ubiquitin protein ligases and phosphorylation-dependent proteolysis. Philos Trans R Soc Lond B Biol Sci. 1999;354:1533-50 pubmed
    ..Here, we review the substrates and pathways regulated by the yeast F-box proteins Cdc4, Grr1 and Met30...
  54. Orlicky S, Tang X, Willems A, Tyers M, Sicheri F. Structural basis for phosphodependent substrate selection and orientation by the SCFCdc4 ubiquitin ligase. Cell. 2003;112:243-56 pubmed
    ..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...
  55. Dixon C, Brunson L, Roy M, Smothers D, Sehorn M, Mathias N. Overproduction of polypeptides corresponding to the amino terminus of the F-box proteins Cdc4p and Met30p inhibits ubiquitin ligase activities of their SCF complexes. Eukaryot Cell. 2003;2:123-33 pubmed
    ..These results suggest a common means to inhibit specific SCF complexes in vivo. ..
  56. Lyons N, Fonslow B, Diedrich J, Yates J, Morgan D. Sequential primed kinases create a damage-responsive phosphodegron on Eco1. Nat Struct Mol Biol. 2013;20:194-201 pubmed publisher
    ..Eco1 activity falls after S phase due to Cdk1-dependent phosphorylation, which triggers ubiquitination by SCF(Cdc4)...
  57. Sanchez M, Calzada A, Bueno A. The Cdc6 protein is ubiquitinated in vivo for proteolysis in Saccharomyces cerevisiae. J Biol Chem. 1999;274:9092-7 pubmed
    ..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 ..
  58. Lyapina S, Correll C, Kipreos E, Deshaies R. Human CUL1 forms an evolutionarily conserved ubiquitin ligase complex (SCF) with SKP1 and an F-box protein. Proc Natl Acad Sci U S A. 1998;95:7451-6 pubmed
    ..SCF is composed of three proteins-ySKP1, CDC53 (Cullin), and the F-box protein CDC4-that are conserved from yeast to humans...
  59. Mittag T, Orlicky S, Choy W, Tang X, Lin H, Sicheri F, et al. Dynamic equilibrium engagement of a polyvalent ligand with a single-site receptor. Proc Natl Acad Sci U S A. 2008;105:17772-7 pubmed publisher
    ..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...
  60. Ivantsiv Y, Kaplun L, Tzirkin Goldin R, Shabek N, Raveh D. Unique role for the UbL-UbA protein Ddi1 in turnover of SCFUfo1 complexes. Mol Cell Biol. 2006;26:1579-88 pubmed
    ..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. ..
  61. Li T, Pavletich N, Schulman B, Zheng N. High-level expression and purification of recombinant SCF ubiquitin ligases. Methods Enzymol. 2005;398:125-42 pubmed
    ..We propose that similar approaches can be used to obtain large quantities of other SCF and SCF-like complexes for biochemical and structural investigations. ..
  62. Vendrell A, Martínez Pastor M, Gonzalez Novo A, Pascual Ahuir A, Sinclair D, Proft M, et al. Sir2 histone deacetylase prevents programmed cell death caused by sustained activation of the Hog1 stress-activated protein kinase. EMBO Rep. 2011;12:1062-8 pubmed publisher
    ..Mutations of the SCF(CDC4) ubiquitin ligase complex suppress cell death by preventing the degradation of Msn2 and Msn4 transcription factors...
  63. Siede W, Friedberg A, Dianova I, Friedberg E. Characterization of G1 checkpoint control in the yeast Saccharomyces cerevisiae following exposure to DNA-damaging agents. Genetics. 1994;138:271-81 pubmed 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)...
  64. Choi W, Clark M, Chen J, Jong A. The CDC4 gene product is associated with the yeast nuclear skeleton. Biochem Biophys Res Commun. 1990;172:1324-30 pubmed
    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...
  65. McLellan J, O Neil N, Tarailo S, Stoepel J, Bryan J, Rose A, et al. Synthetic lethal genetic interactions that decrease somatic cell proliferation in Caenorhabditis elegans identify the alternative RFC CTF18 as a candidate cancer drug target. Mol Biol Cell. 2009;20:5306-13 pubmed publisher
    ..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. ..
  66. Drury L, Diffley J. Factors affecting the diversity of DNA replication licensing control in eukaryotes. Curr Biol. 2009;19:530-5 pubmed publisher
    ..These experiments provide a framework for understanding the diversity of licensing regulation in eukaryotes and provide new tools for manipulating the chromosome-replication cycle. ..
  67. Mittag T, Marsh J, Grishaev A, Orlicky S, Lin H, Sicheri F, et al. Structure/function implications in a dynamic complex of the intrinsically disordered Sic1 with the Cdc4 subunit of an SCF ubiquitin ligase. Structure. 2010;18:494-506 pubmed publisher
    ..One such dynamic complex involves the intrinsically disordered Sic1 with its partner Cdc4 in regulation of yeast cell cycle progression...