HRT1

Summary

Gene Symbol: HRT1
Description: SCF ubiquitin ligase complex subunit HRT1
Alias: HRT2, RBX1, ROC1, SCF ubiquitin ligase complex subunit HRT1
Species: Saccharomyces cerevisiae S288c

Top Publications

  1. Kleiger G, Saha A, Lewis S, Kuhlman B, Deshaies R. Rapid E2-E3 assembly and disassembly enable processive ubiquitylation of cullin-RING ubiquitin ligase substrates. Cell. 2009;139:957-68 pubmed publisher
    ..We discuss different strategies by which processive ubiquitin chain synthesis may be achieved. ..
  2. 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
    ..Mass spectrometric analysis of proteins copurifying with Cdc53 identified the RING-H2 finger protein Hrt1 as a subunit of SCF. Hrt1 shows striking similarity to the Apc11 subunit of anaphase-promoting complex...
  3. 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
    ..This spatial variability may accommodate diverse acceptor lysine geometries in both substrates and the elongating ubiquitin chain and thereby increase catalytic efficiency. ..
  4. 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. ..
  5. Uematsu K, Okumura F, Tonogai S, Joo Okumura A, Alemayehu D, Nishikimi A, et al. ASB7 regulates spindle dynamics and genome integrity by targeting DDA3 for proteasomal degradation. J Cell Biol. 2016;215:95-106 pubmed
    ..Collectively, these data indicate that ASB7 plays a crucial role in regulating spindle dynamics and genome integrity by controlling the expression of DDA3. ..
  6. Ibarra R, Sandoval D, Fredrickson E, Gardner R, Kleiger G. The San1 Ubiquitin Ligase Functions Preferentially with Ubiquitin-conjugating Enzyme Ubc1 during Protein Quality Control. J Biol Chem. 2016;291:18778-90 pubmed publisher
    ..We discuss how these results may have broad implications for the regulation of PQC-mediated protein degradation. ..
  7. Yang X, Zhou J, Sun L, Wei Z, Gao J, Gong W, et al. Structural basis for the function of DCN-1 in protein Neddylation. J Biol Chem. 2007;282:24490-4 pubmed
    ..The structural and biochemical results are consistent with the role of DCN-1 as a scaffold protein in a multisubunit neddylation E3 ligase complex. ..
  8. Michel J, McCarville J, Xiong Y. A role for Saccharomyces cerevisiae Cul8 ubiquitin ligase in proper anaphase progression. J Biol Chem. 2003;278:22828-37 pubmed
    ..Cul8 but not by any other yeast or human cullins, nor by a cul8 mutant deficient in binding to RING finger protein Roc1. Deletion of the RAD9 gene suppressed the anaphase delay phenotype of cul8delta, suggesting that loss of Cul8 ..
  9. 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
    ..These features account for the observed phosphorylation threshold in Sic1 recognition and suggest an equilibrium binding mode between a single receptor site in Cdc4 and multiple low-affinity CPD sites in Sic1. ..

More Information

Publications38

  1. 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
    ..Using a genetic screen, we have isolated a novel allele of the HRT1/RBX1 gene in budding yeast (hrt1-C81Y)...
  2. 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
    ..Cln1 was ubiquitinated by SCF (Skp1-Cdc53-F-box protein) complexes containing the F-box protein Grr1, Rbx1, and the E2 Cdc34...
  3. Morohashi H, Maculins T, Labib K. The amino-terminal TPR domain of Dia2 tethers SCF(Dia2) to the replisome progression complex. Curr Biol. 2009;19:1943-9 pubmed publisher
    ..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. ..
  4. 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
    ..Here we demonstrate a variant mechanism, whereby the E2 Ubc12 functions with two E3s, Hrt1 and Dcn1, for ligation of the UBL Rub1 to Cdc53's WHB subdomain...
  5. 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
    ..We discuss implications of this finding for function of other ubiquitin ligases. ..
  6. Kurz T, Ozlu N, Rudolf F, O Rourke S, Luke B, Hofmann K, et al. The conserved protein DCN-1/Dcn1p is required for cullin neddylation in C. elegans and S. cerevisiae. Nature. 2005;435:1257-61 pubmed
    ..Cullins, together with the RING-finger protein Rbx1, form the catalytic core of the ligase, and recruit the substrate-recognition module...
  7. Zachariae W, Nasmyth K. Whose end is destruction: cell division and the anaphase-promoting complex. Genes Dev. 1999;13:2039-58 pubmed
  8. Sakata T, Fujii K, Ohno M, Kitabatake M. Crt10 directs the cullin-E3 ligase Rtt101 to nonfunctional 25S rRNA decay. Biochem Biophys Res Commun. 2015;457:90-4 pubmed publisher
    ..Our results showed the convergence of multiple pathways for stresses that harm nucleic acids and provided a molecular framework for the substrate diversity of the E3 complex. ..
  9. Kurz T, Chou Y, Willems A, Meyer Schaller N, Hecht M, Tyers M, et al. Dcn1 functions as a scaffold-type E3 ligase for cullin neddylation. Mol Cell. 2008;29:23-35 pubmed publisher
    ..We show that Dcn1 is necessary and sufficient for cullin neddylation in a purified recombinant system. Taken together, these data demonstrate that Dcn1 is a scaffold-like E3 ligase for cullin neddylation. ..
  10. 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
    ..The complementary C-terminal segment of SIC1 binds to the S-phase cyclin CLB5, indicating a modular structure for SIC1. ..
  11. Harreman M, Taschner M, Sigurdsson S, Anindya R, Reid J, Somesh B, et al. Distinct ubiquitin ligases act sequentially for RNA polymerase II polyubiquitylation. Proc Natl Acad Sci U S A. 2009;106:20705-10 pubmed publisher
  12. Somesh B, Reid J, Liu W, Søgaard T, Erdjument Bromage H, Tempst P, et al. Multiple mechanisms confining RNA polymerase II ubiquitylation to polymerases undergoing transcriptional arrest. Cell. 2005;121:913-23 pubmed
    ..These results identify several mechanisms that confine ubiquitylation of RNAPII to the forms of the enzyme that arrest during elongation. ..
  13. 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
    ..SCF complexes couple protein kinase signaling pathways to the control of protein abundance. ..
  14. Sadhu M, Moresco J, Zimmer A, Yates J, Rine J. Multiple inputs control sulfur-containing amino acid synthesis in Saccharomyces cerevisiae. Mol Biol Cell. 2014;25:1653-65 pubmed publisher
    ..This modification could be involved in the nutritional control of SCF(Met30) activity toward Met4. ..
  15. 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
    ..The core SCF subunits Cdc53, Hrt1 and Skp1 were distributed in the nucleus and the cytoplasm, whereas the F-box protein Cdc4 was exclusively nuclear...
  16. Starita L, Lo R, Eng J, von Haller P, Fields S. Sites of ubiquitin attachment in Saccharomyces cerevisiae. Proteomics. 2012;12:236-40 pubmed publisher
    ..However, such peptides with GG shifts have been difficult to discover. We identify 870 unique sites of ubiquitin attachment on 438 different proteins of the yeast Saccharomyces cerevisiae. ..
  17. 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
    ..The phosphorylation-dependent elimination of Ash1 by the ubiquitin-proteasome system thus underpins developmental asymmetry in budding yeast. ..
  18. 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. ..
  19. 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
  20. Rabut G, Le Dez G, Verma R, Makhnevych T, Knebel A, Kurz T, et al. The TFIIH subunit Tfb3 regulates cullin neddylation. Mol Cell. 2011;43:488-95 pubmed publisher
    ..Surprisingly, proper modification of Rtt101 neither correlated with catalytic activity of the RING domain of Hrt1 nor required the Nedd8 ligase Dcn1...
  21. Liu Y, Mimura S, Kishi T, Kamura T. A longevity protein, Lag2, interacts with SCF complex and regulates SCF function. EMBO J. 2009;28:3366-77 pubmed publisher
    ..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. ..
  22. 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
    ..These insights to the G protein signaling network reveal the essential genome as an untapped resource for identifying new components and regulators of signal transduction pathways. ..
  23. Siergiejuk E, Scott D, Schulman B, Hofmann K, Kurz T, Peter M. Cullin neddylation and substrate-adaptors counteract SCF inhibition by the CAND1-like protein Lag2 in Saccharomyces cerevisiae. EMBO J. 2009;28:3845-56 pubmed publisher
    ..Our results favour a model in which binding of substrate-specific adaptors triggers release of Cand1/Lag2, whereas subsequent neddylation of the cullin facilitates the removal and prevents re-association of Lag2/Cand1. ..
  24. Ohta T, Michel J, Schottelius A, Xiong Y. ROC1, a homolog of APC11, represents a family of cullin partners with an associated ubiquitin ligase activity. Mol Cell. 1999;3:535-41 pubmed
    We have identified two highly conserved RING finger proteins, ROC1 and ROC2, that are homologous to APC11, a subunit of the anaphase-promoting complex...
  25. 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
    ..Our results show that there is no fundamental barrier to obtaining specific inhibitors to modulate function of individual SCF complexes. ..
  26. Han J, Li Q, McCullough L, Kettelkamp C, Formosa T, Zhang Z. Ubiquitylation of FACT by the cullin-E3 ligase Rtt101 connects FACT to DNA replication. Genes Dev. 2010;24:1485-90 pubmed publisher
    ..Origin function is compromised in cells lacking Rtt101 or with an Spt16 mutation. These findings identify Spt16 as an Rtt101 substrate, and suggest that Spt16 ubiquitylation is important for FACT to function during DNA replication. ..
  27. 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
    ..Here it is shown that the endogenous VHL complex in rat liver also includes Rbx1, an evolutionarily conserved protein that contains a RING-H2 fingerlike motif and that interacts with Cullins...
  28. 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
    ..Composite dynamic interactions of low affinity sites may be a general mechanism to establish phosphorylation thresholds in biological responses. ..
  29. 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
    ..Ubc4 thus interacts with multiple SCFs in vitro, and the interactions among SCF and E2 components of the ubiquitination machinery may allow further diversification of the roles of SCFs in vivo. ..