SIC1

Summary

Gene Symbol: SIC1
Description: cyclin-dependent protein serine/threonine kinase inhibiting protein SIC1
Alias: BYC1, SDB25, cyclin-dependent protein serine/threonine kinase inhibiting protein SIC1
Species: Saccharomyces cerevisiae S288c
Products:     SIC1

Top Publications

  1. Lengronne A, Schwob E. The yeast CDK inhibitor Sic1 prevents genomic instability by promoting replication origin licensing in late G(1). Mol Cell. 2002;9:1067-78 pubmed
    ..Here we show that yeast lacking the CDK inhibitor Sic1 initiate DNA replication from fewer origins, have an extended S phase, and inefficiently separate sister chromatids ..
  2. Wasch R, Cross F. APC-dependent proteolysis of the mitotic cyclin Clb2 is essential for mitotic exit. Nature. 2002;418:556-62 pubmed
    ..and activation of the APC regulatory subunit Cdh1 (also known as Hct1) and the cyclin-dependent kinase inhibitor Sic1 by the phosphatase Cdc14, allowing mitotic kinase inactivation and mitotic exit...
  3. 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
    ..Deletion of SIC1 allows these mutants to replicate...
  4. 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. ..
  5. 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
    ..the Cdc53-containing SCFCdc4 ubiquitin ligase required for ubiquitination of the cyclin-dependent kinase inhibitor Sic1 and for the G1 to S cell cycle transition...
  6. Mendenhall M. An inhibitor of p34CDC28 protein kinase activity from Saccharomyces cerevisiae. Science. 1993;259:216-9 pubmed
    ..The p40 protein bound tightly to p34CDC28 and inhibited the activity of the kinase. The p40 protein may provide another mechanism to regulate p34CDC28 protein kinase activity. ..
  7. Wang Y, Hu F, Elledge S. The Bfa1/Bub2 GAP complex comprises a universal checkpoint required to prevent mitotic exit. Curr Biol. 2000;10:1379-82 pubmed
    ..the Cdh1 component of the anaphase-promoting complex to degrade cyclin B (Clb) and inducing the CDK inhibitor Sic1 to inactivate Cdk1 [2]...
  8. Yuste Rojas M, Cross F. Mutations in CDC14 result in high sensitivity to cyclin gene dosage in Saccharomyces cerevisiae. Mol Gen Genet. 2000;263:60-72 pubmed
    ..the idea that cdc14 mutations elevate Clb-Cdc28 kinase activity, deletion of the gene for the Clb-Cdc28 inhibitor Sic1 caused synthetic lethality with cdc14-1, as did the deletion of HCT1, which is required for proteolysis of Clb2p...
  9. Kõivomägi M, Valk E, Venta R, Iofik A, Lepiku M, Balog E, et al. Cascades of multisite phosphorylation control Sic1 destruction at the onset of S phase. Nature. 2011;480:128-31 pubmed publisher
    ..to be governed by complexes of Cdk1 and Cln cyclins that phosphorylate six or more sites on the Clb5-Cdk1 inhibitor Sic1, directing it to SCF-mediated destruction. The resulting Sic1-free Clb5-Cdk1 complex triggers S phase...

More Information

Publications73

  1. Petroski M, Deshaies R. Context of multiubiquitin chain attachment influences the rate of Sic1 degradation. Mol Cell. 2003;11:1435-44 pubmed
    ..Here we define the minimal signal for the degradation of the S phase CDK inhibitor Sic1. Of 20 lysines scattered throughout Sic1, 6 N-terminal lysines serve as major ubiquitination sites...
  2. Edgington N, Futcher B. Relationship between the function and the location of G1 cyclins in S. cerevisiae. J Cell Sci. 2001;114:4599-611 pubmed
    ..Cln2 was found in both nucleus and cytoplasm. A substrate of Cln2, Sic1, was also in both compartments. Cytoplasmic Cln2 was concentrated at sites of polarized growth...
  3. 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
    ..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) allele in yeast ..
  4. Visintin R, Craig K, Hwang E, Prinz S, Tyers M, Amon A. The phosphatase Cdc14 triggers mitotic exit by reversal of Cdk-dependent phosphorylation. Mol Cell. 1998;2:709-18 pubmed
    ..Cdc14 dephosphorylates Sic1, a Cdk inhibitor, and Swi5, a transcription factor for SIC1, and induces degradation of mitotic cyclins, likely by ..
  5. 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 Sic1 degrons, each capable of high-affinity ..
  6. Fitzpatrick P, Toyn J, Millar J, Johnston L. DNA replication is completed in Saccharomyces cerevisiae cells that lack functional Cdc14, a dual-specificity protein phosphatase. Mol Gen Genet. 1998;258:437-41 pubmed
    ..Furthermore, in a promoter shut-off experiment, cells lacking Cdc14 appear to carry out a normal S phase. Thus Cdc14 functions mainly in late mitosis and it has no essential role in S phase. ..
  7. Barberis M, Pagano M, Gioia L, Marin O, Vanoni M, Pinna L, et al. CK2 regulates in vitro the activity of the yeast cyclin-dependent kinase inhibitor Sic1. Biochem Biophys Res Commun. 2005;336:1040-8 pubmed
    We have previously demonstrated that the cyclin-dependent kinase inhibitor (Cki) Sic1 of Saccharomyces cerevisiae is phosphorylated in vitro by the CK2 kinase on Ser(201) residue...
  8. Verma R, McDonald H, Yates J, Deshaies R. Selective degradation of ubiquitinated Sic1 by purified 26S proteasome yields active S phase cyclin-Cdk. Mol Cell. 2001;8:439-48 pubmed
    ..We report that ubiquitinated Sic1 (Ub-Sic1) embedded within inactive S phase cyclin-Cdk (S-Cdk) complexes was rapidly degraded by purified 26S ..
  9. 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
    ..In newborn G(1) cells, Clb kinase accumulation is blocked, in part because of the Sic1 stoichiometric inhibitor...
  10. Meitinger F, Petrova B, Lombardi I, Bertazzi D, Hub B, Zentgraf H, et al. Targeted localization of Inn1, Cyk3 and Chs2 by the mitotic-exit network regulates cytokinesis in budding yeast. J Cell Sci. 2010;123:1851-61 pubmed publisher
    ..This defect was partially suppressed by increased levels of Cyk3. We therefore propose that the MEN directly controls cytokinesis via targeting of Inn1, Cyk3 and Chs2 to the bud neck...
  11. Menoyo S, Ricco N, Bru S, Hernandez Ortega S, Escote X, Aldea M, et al. Phosphate-activated cyclin-dependent kinase stabilizes G1 cyclin to trigger cell cycle entry. Mol Cell Biol. 2013;33:1273-84 pubmed publisher
    ..Taken together, our data indicate that Cln3 is a molecular target of the Pho85 kinase that is required to modulate cell cycle entry in response to environmental changes in nutrient availability. ..
  12. Barberis M, Linke C, Adrover M, Gonzalez Novo A, Lehrach H, Krobitsch S, et al. Sic1 plays a role in timing and oscillatory behaviour of B-type cyclins. Biotechnol Adv. 2012;30:108-30 pubmed publisher
    ..The transition from low to high Clb activity is triggered by degradation of Sic1, the inhibitor of Cdk1-Clb complexes, at the entry to S phase...
  13. 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
    ..Conditional inactivation of hrt1(ts) results in stabilization of the SCFCdc4 substrates Sic1 and Cln2 and cell cycle arrest at G1/S...
  14. 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...
  15. Dirick L, Goetsch L, Ammerer G, Byers B. Regulation of meiotic S phase by Ime2 and a Clb5,6-associated kinase in Saccharomyces cerevisiae. Science. 1998;281:1854-7 pubmed
    ..Meiosis differs instead in the mechanism that controls removal of the Cdk inhibitor Sic1. Destruction of Sic1 and activation of a Clb5-dependent kinase in meiotic cells required the action of the meiosis-..
  16. 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
    ..Initiation of DNA replication in yeast requires elimination of the cyclin-dependent kinase inhibitor Sic1 via the SCF(Cdc4) ubiquitin ligase...
  17. McGrath D, Balog E, Kõivomägi M, Lucena R, Mai M, Hirschi A, et al. Cks confers specificity to phosphorylation-dependent CDK signaling pathways. Nat Struct Mol Biol. 2013;20:1407-14 pubmed publisher
    ..Together, our results portray Cks as a multifunctional phosphoadaptor that serves as a specificity factor for CDK activity. ..
  18. 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. ..
  19. Barberis M, De Gioia L, Ruzzene M, Sarno S, Coccetti P, Fantucci P, et al. The yeast cyclin-dependent kinase inhibitor Sic1 and mammalian p27Kip1 are functional homologues with a structurally conserved inhibitory domain. Biochem J. 2005;387:639-47 pubmed
    In Saccharomyces cerevisiae, Sic1, an inhibitor of Cdk (cyclin-dependent kinase), blocks the activity of S-Cdk1 (Cdk1/Clb5,6) kinase that is required for DNA replication...
  20. Donovan J, Toyn J, Johnson A, Johnston L. P40SDB25, a putative CDK inhibitor, has a role in the M/G1 transition in Saccharomyces cerevisiae. Genes Dev. 1994;8:1640-53 pubmed
    ..We have isolated SDB25, a high copy suppressor of temperature-sensitive dbf2 mutants, and genetic analysis suggests that the two proteins ..
  21. Sawarynski K, Najor N, Kepsel A, Brush G. Sic1-induced DNA rereplication during meiosis. Proc Natl Acad Sci U S A. 2009;106:232-7 pubmed publisher
    ..in Saccharomyces cerevisiae through meiosis-specific induction of the cyclin-dependent kinase (CDK) inhibitor Sic1 mutated at multiple phosphorylation sites...
  22. 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
    ..G1 to S-phase in cycling cells of budding yeast is dependent on the destruction of the S-phase cyclin/CDK inhibitor SIC1. Genetic data suggest that SIC1 proteolysis is mediated by the ubiquitin pathway and requires the action of CDC34, ..
  23. 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
    ..The initiation of DNA replication in Saccharomyces cerevisiae depends upon the destruction of the Clb-Cdc28 inhibitor Sic1. In proliferating cells Cln-Cdc28 complexes phosphorylate Sic1, which stimulates binding of Sic1 to SCF(Cdc4) and ..
  24. Coccetti P, Tripodi F, Tedeschi G, Nonnis S, Marin O, Fantinato S, et al. The CK2 phosphorylation of catalytic domain of Cdc34 modulates its activity at the G1 to S transition in Saccharomyces cerevisiae. Cell Cycle. 2008;7:1391-401 pubmed
  25. 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
    ..ligase SCF(Cdc4) (Skp1/Cul1/F-box protein) recognizes its substrate, the cyclin-dependent kinase inhibitor Sic1, in a multisite phosphorylation-dependent manner...
  26. Verma R, Annan R, Huddleston M, Carr S, Reynard G, Deshaies R. Phosphorylation of Sic1p by G1 Cdk required for its degradation and entry into S phase. Science. 1997;278:455-60 pubmed
    ..These data suggest a molecular model of how phosphorylation and proteolysis cooperate to bring about the G1/S transition in budding yeast. ..
  27. Tyers M. The cyclin-dependent kinase inhibitor p40SIC1 imposes the requirement for Cln G1 cyclin function at Start. Proc Natl Acad Sci U S A. 1996;93:7772-6 pubmed
    ..I report here that cln cells are rendered viable by deletion of SIC1. Conversely, in cln1 cln2 cells, which have low CLN activity, modest increases in SIC1 gene dosage cause ..
  28. Schneider B, Yang Q, Futcher A. Linkage of replication to start by the Cdk inhibitor Sic1. Science. 1996;272:560-2 pubmed
    ..In Saccharomyces cerevisiae, three G1 cyclins (Clns) are important for Start, the event committing cells to division. Sic1, an inhibitor of C1b-Cdc28 kinases, became phosphorylated at Start, and this phosphorylation depended on the ..
  29. 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
    ..Disruption of the D domain compromises the activity of yeast SCF(Cdc4) toward the CDK inhibitor Sic1 and other substrates...
  30. Barberis M. Molecular systems biology of Sic1 in yeast cell cycle regulation through multiscale modeling. Adv Exp Med Biol. 2012;736:135-67 pubmed publisher
    ..and computational studies have been employed to investigate structure, function and temporal dynamics of the Cki Sic1 that regulates cell cycle progression in Saccharomyces cerevisiae...
  31. Verma R, Oania R, Graumann J, Deshaies R. Multiubiquitin chain receptors define a layer of substrate selectivity in the ubiquitin-proteasome system. Cell. 2004;118:99-110 pubmed
    ..We addressed this issue by analyzing degradation of the ubiquitinated Cdk inhibitor Sic1 (UbSic1) in vitro. Mutant rpn10Delta and rad23Delta proteasomes failed to bind or degrade UbSic1...
  32. Sawarynski K, Kaplun A, Tzivion G, Brush G. Distinct activities of the related protein kinases Cdk1 and Ime2. Biochim Biophys Acta. 2007;1773:450-6 pubmed
    ..to DNA replication during the normal cell cycle requires degradation of the cyclin-dependent kinase (CDK) inhibitor Sic1. The G1 cyclin-CDK complexes Cln1-Cdk1 and Cln2-Cdk1 initiate the process of Sic1 removal by directly catalyzing ..
  33. Schwab M, Lutum A, Seufert W. Yeast Hct1 is a regulator of Clb2 cyclin proteolysis. Cell. 1997;90:683-93 pubmed
    ..Viability of hct1 mutants depends on SIC1. This and further results suggest that inhibition of cyclin-dependent kinases may compensate for defects in cyclin ..
  34. Archambault V, Li C, Tackett A, Wasch R, Chait B, Rout M, et al. Genetic and biochemical evaluation of the importance of Cdc6 in regulating mitotic exit. Mol Biol Cell. 2003;14:4592-604 pubmed
    ..During late mitosis, Cdc6 is present at levels comparable with Sic1 and binds specifically to the mitotic cyclin Clb2...
  35. 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
    We have reconstituted the ubiquitination pathway for the Cdk inhibitor Sic1 using recombinant proteins...
  36. Aerne B, Johnson A, Toyn J, Johnston L. Swi5 controls a novel wave of cyclin synthesis in late mitosis. Mol Biol Cell. 1998;9:945-56 pubmed
    We have shown previously that the Swi5 transcription factor regulates the expression of the SIC1 Cdk inhibitor in late mitosis. This suggests that Swi5 might control other genes with roles in ending mitosis...
  37. Clotet J, Escote X, Adrover M, Yaakov G, Garí E, Aldea M, et al. Phosphorylation of Hsl1 by Hog1 leads to a G2 arrest essential for cell survival at high osmolarity. EMBO J. 2006;25:2338-46 pubmed
    ..of yeast to osmostress leads to activation of the Hog1 SAPK, which controls cell cycle at G1 by the targeting of Sic1. Here, we show that survival to osmostress also requires regulation of G2 progression...
  38. 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
    ..of ubiquitin-charged Cdc34-S - Ub from the RING is essential for ubiquitination of the SCF(Cdc4)-bound substrate Sic1. Release of ubiquitin-charged E2 from E3 prior to ubiquitin transfer is a previously unrecognized step in ..
  39. Jaspersen S, Charles J, Tinker Kulberg R, Morgan D. A late mitotic regulatory network controlling cyclin destruction in Saccharomyces cerevisiae. Mol Biol Cell. 1998;9:2803-17 pubmed
    ..mutants and found that the growth defect in most of the mutants is suppressed by overexpression of SPO12, YAK1, and SIC1 and is exacerbated by overproduction of the mitotic cyclin Clb2...
  40. 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
    ..By studying the polyubiquitination of Sic1 by the E2 protein Cdc34 and the RING E3 Skp1/Cul1/F-box (SCF) protein, we now demonstrate that in addition to E2/E3-..
  41. Wang Y, Shirogane T, Liu D, Harper J, Elledge S. Exit from exit: resetting the cell cycle through Amn1 inhibition of G protein signaling. Cell. 2003;112:697-709 pubmed
    ..Thus, Amn1 is part of a daughter-specific switch that helps cells exit from mitotic exit and reset the cell cycle. ..
  42. Charles J, Jaspersen S, Tinker Kulberg R, Hwang L, Szidon A, Morgan D. The Polo-related kinase Cdc5 activates and is destroyed by the mitotic cyclin destruction machinery in S. cerevisiae. Curr Biol. 1998;8:497-507 pubmed
    ..We conclude that Cdc5 is a positive regulator of cyclin-specific APC activity in late mitosis. Degradation of Cdc5 in G1 might provide a feedback mechanism by which the APC destroys its activator at the onset of the next cell cycle. ..
  43. Gruneberg U, Campbell K, Simpson C, Grindlay J, Schiebel E. Nud1p links astral microtubule organization and the control of exit from mitosis. EMBO J. 2000;19:6475-88 pubmed
    ..Thus, in nud1-2 cells the failure of Tem1p to interact with Cdc15p at the SPB probably prevents mitotic exit. ..
  44. Bailly E, Reed S. Functional characterization of rpn3 uncovers a distinct 19S proteasomal subunit requirement for ubiquitin-dependent proteolysis of cell cycle regulatory proteins in budding yeast. Mol Cell Biol. 1999;19:6872-90 pubmed
    ..but consistent with the lack of a G(1) arrest phenotype in thermosensitive rpn3 strains, the Cdk inhibitor Sic1 exhibits a short half-life regardless of the RPN3 genotype...
  45. Coccetti P, Zinzalla V, Tedeschi G, Russo G, Fantinato S, Marin O, et al. Sic1 is phosphorylated by CK2 on Ser201 in budding yeast cells. Biochem Biophys Res Commun. 2006;346:786-93 pubmed
    We have previously identified Ser201 of Sic1, a yeast cyclin-dependent kinase inhibitor, as an in vitro target of protein kinase CK2...
  46. Ikui A, Archambault V, Drapkin B, Campbell V, Cross F. Cyclin and cyclin-dependent kinase substrate requirements for preventing rereplication reveal the need for concomitant activation and inhibition. Genetics. 2007;175:1011-22 pubmed
  47. Pathak R, Blank H, Guo J, Ellis S, Polymenis M. The Dcr2p phosphatase destabilizes Sic1p in Saccharomyces cerevisiae. Biochem Biophys Res Commun. 2007;361:700-4 pubmed
    ..Our results identify a novel factor that affects the stability of Sic1p, possibly contributing to mechanisms that trigger initiation of cell division. ..
  48. Tripodi F, Zinzalla V, Vanoni M, Alberghina L, Coccetti P. In CK2 inactivated cells the cyclin dependent kinase inhibitor Sic1 is involved in cell-cycle arrest before the onset of S phase. Biochem Biophys Res Commun. 2007;359:921-7 pubmed
    ..We have previously shown that Sic1, the inhibitor of Clb5-Cdc28 complexes required for the G1/S transition, is a physiologically relevant CK2 ..
  49. Bhaduri S, Valk E, Winters M, Gruessner B, Loog M, Pryciak P. A docking interface in the cyclin Cln2 promotes multi-site phosphorylation of substrates and timely cell-cycle entry. Curr Biol. 2015;25:316-25 pubmed publisher
    ..Furthermore, this docking function helps ensure full phosphorylation of substrates with multiple phosphorylation sites, and this contributes to punctual cell-cycle entry. ..
  50. Kito K, Kawaguchi N, Okada S, Ito T. Discrimination between stable and dynamic components of protein complexes by means of quantitative proteomics. Proteomics. 2008;8:2366-70 pubmed publisher
    ..We successfully applied this strategy to analyze two yeast protein complexes, eIF2B-eIF2 and cyclin-Cdc28. ..
  51. 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
    ..In addition, we have determined that Sic1, a Clb/Cdc28-specific inhibitor, is the SCF(Cdc4) target that inhibits spindle pole separation in cells lacking ..
  52. Brush G, Najor N, Dombkowski A, Cukovic D, Sawarynski K. Yeast IME2 functions early in meiosis upstream of cell cycle-regulated SBF and MBF targets. PLoS ONE. 2012;7:e31575 pubmed publisher
    ..These two CDK complexes directly catalyze phosphorylation of the B-type cyclin/CDK inhibitor Sic1 during the cell cycle to enable its destruction...
  53. Lass A, Cocklin R, Scaglione K, Skowyra M, Korolev S, Goebl M, et al. The loop-less tmCdc34 E2 mutant defective in polyubiquitination in vitro and in vivo supports yeast growth in a manner dependent on Ubp14 and Cka2. Cell Div. 2011;6:7 pubmed publisher
    ..The in vitro defect in Sic1 substrate polyubiquitination is similar to the defect observed in reactions with ?12Cdc34 that cannot support ..
  54. Nishizawa M, Kawasumi M, Fujino M, Toh e A. Phosphorylation of sic1, a cyclin-dependent kinase (Cdk) inhibitor, by Cdk including Pho85 kinase is required for its prompt degradation. Mol Biol Cell. 1998;9:2393-405 pubmed
    In the yeast Saccharomyces cerevisiae, Sic1, an inhibitor of Clb-Cdc28 kinases, must be phosphorylated and degraded in G1 for cells to initiate DNA replication, and Cln-Cdc28 kinase appears to be primarily responsible for phosphorylation ..
  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. Cocklin R, Heyen J, Larry T, Tyers M, Goebl M. New insight into the role of the Cdc34 ubiquitin-conjugating enzyme in cell cycle regulation via Ace2 and Sic1. Genetics. 2011;187:701-15 pubmed publisher
    ..levels of regulation of the Ace2 transcription factor and the cyclin-dependent protein kinase inhibitor Sic1. In cells carrying the Cdc34(tm) mutation, which alters the conserved sequence, the cyclin-dependent protein kinase ..
  57. Manfrini N, Gobbini E, Baldo V, Trovesi C, Lucchini G, Longhese M. G(1)/S and G(2)/M cyclin-dependent kinase activities commit cells to death in the absence of the S-phase checkpoint. Mol Cell Biol. 2012;32:4971-85 pubmed publisher
    ..Moreover, these findings suggest that the essential function of Mec1 and Rad53 is not necessarily separated from the function of these kinases in supporting DNA synthesis under stress conditions. ..
  58. Deng C, Saunders W. RIM4 encodes a meiotic activator required for early events of meiosis in Saccharomyces cerevisiae. Mol Genet Genomics. 2001;266:497-504 pubmed
    ..Furthermore, rim4Delta mutants show defects in premeiotic DNA synthesis, which can be suppressed by deletion of the SIC1 gene, which encodes a Cdk inhibitor...
  59. de Bruin R, Kalashnikova T, Wittenberg C. Stb1 collaborates with other regulators to modulate the G1-specific transcriptional circuit. Mol Cell Biol. 2008;28:6919-28 pubmed publisher
    ..The repression during G(1) also depends upon Sin3. We speculate that the interaction between Stb1 and Sin3 regulates the Sin3/HDAC complex at G(1)-specific promoters. ..
  60. Saeki Y, Kudo T, Sone T, Kikuchi Y, Yokosawa H, Toh e A, et al. Lysine 63-linked polyubiquitin chain may serve as a targeting signal for the 26S proteasome. EMBO J. 2009;28:359-71 pubmed publisher
    ..These results raise the possibility that Lys63-linked ubiquitin chain also serves as a targeting signal for the 26S proteaseome in vivo. ..
  61. Shah R, Jensen S, Frenz L, Johnson A, Johnston L. The Spo12 protein of Saccharomyces cerevisiae: a regulator of mitotic exit whose cell cycle-dependent degradation is mediated by the anaphase-promoting complex. Genetics. 2001;159:965-80 pubmed
    ..of Clb-Cdc28 activity and can function independently of either the cyclin-dependent kinase inhibitor (CDKi), Sic1, or the anaphase-promoting complex (APC) regulator, Hct1...
  62. Hanna J, Waterman D, Isasa M, Elsasser S, Shi Y, Gygi S, et al. Cuz1/Ynl155w, a zinc-dependent ubiquitin-binding protein, protects cells from metalloid-induced proteotoxicity. J Biol Chem. 2014;289:1876-85 pubmed publisher
    ..Thus, Cuz1/Ynl155w is proposed to protect cells from metalloid-induced proteotoxicity by delivering ubiquitinated substrates to Cdc48 and the proteasome for destruction. ..
  63. Rødkær S, Pultz D, Brusch M, Bennetzen M, Falkenby L, Andersen J, et al. Quantitative proteomics identifies unanticipated regulators of nitrogen- and glucose starvation. Mol Biosyst. 2014;10:2176-88 pubmed publisher
    ..By bioinformatics and network analyses, we have identified the cyclin-dependent kinase (CDK) inhibitor Sic1, the Hsp90 co-chaperone Cdc37, and the Hsp90 isoform Hsp82 to putatively mediate some of the starvation responses...
  64. Jacobson M, Muñoz C, Knox K, Williams B, Lu L, Cross F, et al. Mutations in SID2, a novel gene in Saccharomyces cerevisiae, cause synthetic lethality with sic1 deletion and may cause a defect during S phase. Genetics. 2001;159:17-33 pubmed
    b>SIC1 encodes a nonessential B-type cyclin/CDK inhibitor that functions at the G1/S transition and the exit from mitosis...