SIC1 is Ubiquitinated in Vitro by a Pathway That Requires CDC4, CDC34, and Cyclin/CDK Activities

Overview

Journal Mol Biol Cell

Specialties Cell Biology
Molecular Biology

Date 1997 Aug 1

PMID 9285816

Citations 87

Authors

R Verma

R M Feldman

R J Deshaies

Affiliations

Soon will be listed here.

Abstract

Traversal from 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, CDC4, CDC53, SKP1, and CLN/CDC28. As a first step in defining the functions of the corresponding gene products, we have reconstituted SIC1 multiubiquitination in DEAE-fractionated yeast extract. Multiubiquitination depends on cyclin/CDC28 protein kinase and the CDC34 ubiquitin-conjugating enzyme. Ubiquitin chain formation is abrogated in cdc4ts mutant extracts and assembly restored by the addition of exogenous CDC4, suggesting a direct role for this protein in SIC1 multiubiquitination. Deletion analysis of SIC1 indicates that the N-terminal 160 residues are both necessary and sufficient to serve as substrate for CDC34-dependent ubiquitination. The complementary C-terminal segment of SIC1 binds to the S-phase cyclin CLB5, indicating a modular structure for SIC1.

Citing Articles

Modeling the START transition in the budding yeast cell cycle.

Ravi J, Samart K, Zwolak J PLoS Comput Biol. 2024; 20(8):e1012048.

PMID: 39093881 PMC: 11324117. DOI: 10.1371/journal.pcbi.1012048.

Cullin-RING ligases employ geometrically optimized catalytic partners for substrate targeting.

Li J, Purser N, Liwocha J, Scott D, Byers H, Steigenberger B Mol Cell. 2024; 84(7):1304-1320.e16.

PMID: 38382526 PMC: 10997478. DOI: 10.1016/j.molcel.2024.01.022.

Stigma/Style Cell-Cycle Inhibitor 1, a Regulator of Cell Proliferation, Interacts With a Specific 14-3-3 Protein and Is Degraded During Cell Division.

Strini E, Bertolino L, San Martin J, Souza H, Pessotti F, Pinoti V Front Plant Sci. 2022; 13:857745.

PMID: 35444668 PMC: 9013909. DOI: 10.3389/fpls.2022.857745.

Cdc6 is sequentially regulated by PP2A-Cdc55, Cdc14, and Sic1 for origin licensing in .

Philip J, Ord M, Silva A, Singh S, Diffley J, Remus D Elife. 2022; 11.

PMID: 35142288 PMC: 8830886. DOI: 10.7554/eLife.74437.

Ubiquitin-Conjugating Enzymes in Cancer.

Bui Q, Hong J, Kwak M, Lee J, Lee P Cells. 2021; 10(6).

PMID: 34199813 PMC: 8227520. DOI: 10.3390/cells10061383.

References

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(2):233-44. DOI: 10.1016/0092-8674(94)90193-7. View

Verma R, Chi Y, Deshaies R . Cell-free ubiquitination of cell cycle regulators in budding yeast extracts. Methods Enzymol. 1997; 283:366-76. DOI: 10.1016/s0076-6879(97)83030-3. View

Scheffner M, Nuber U, Huibregtse J . Protein ubiquitination involving an E1-E2-E3 enzyme ubiquitin thioester cascade. Nature. 1995; 373(6509):81-3. DOI: 10.1038/373081a0. View

Deshaies R, Chau V, Kirschner M . Ubiquitination of the G1 cyclin Cln2p by a Cdc34p-dependent pathway. EMBO J. 1995; 14(2):303-12. PMC: 398084. DOI: 10.1002/j.1460-2075.1995.tb07004.x. View

Deshaies R, Kirschner M . G1 cyclin-dependent activation of p34CDC28 (Cdc28p) in vitro. Proc Natl Acad Sci U S A. 1995; 92(4):1182-6. PMC: 42662. DOI: 10.1073/pnas.92.4.1182. View

Hochstrasser M . Ubiquitin, proteasomes, and the regulation of intracellular protein degradation. Curr Opin Cell Biol. 1995; 7(2):215-23. DOI: 10.1016/0955-0674(95)80031-x. View

Kellogg D, Kikuchi A, Turck C, Murray A . Members of the NAP/SET family of proteins interact specifically with B-type cyclins. J Cell Biol. 1995; 130(3):661-73. PMC: 2120524. DOI: 10.1083/jcb.130.3.661. View

Zhang H, Kobayashi R, Galaktionov K, Beach D . p19Skp1 and p45Skp2 are essential elements of the cyclin A-CDK2 S phase kinase. Cell. 1995; 82(6):915-25. DOI: 10.1016/0092-8674(95)90271-6. View

Dirick L, Bohm T, Nasmyth K . Roles and regulation of Cln-Cdc28 kinases at the start of the cell cycle of Saccharomyces cerevisiae. EMBO J. 1995; 14(19):4803-13. PMC: 394578. DOI: 10.1002/j.1460-2075.1995.tb00162.x. View

10.

Wall M, Coleman D, Lee E, Posner B, GILMAN A, Sprang S . The structure of the G protein heterotrimer Gi alpha 1 beta 1 gamma 2. Cell. 1995; 83(6):1047-58. DOI: 10.1016/0092-8674(95)90220-1. View

11.

Lambright D, Sondek J, Bohm A, Skiba N, Hamm H, SIGLER P . The 2.0 A crystal structure of a heterotrimeric G protein. Nature. 1996; 379(6563):311-9. DOI: 10.1038/379311a0. View

12.

Sondek J, Bohm A, Lambright D, Hamm H, SIGLER P . Crystal structure of a G-protein beta gamma dimer at 2.1A resolution. Nature. 1996; 379(6563):369-74. DOI: 10.1038/379369a0. View

13.

Koch C, Schleiffer A, Ammerer G, Nasmyth K . Switching transcription on and off during the yeast cell cycle: Cln/Cdc28 kinases activate bound transcription factor SBF (Swi4/Swi6) at start, whereas Clb/Cdc28 kinases displace it from the promoter in G2. Genes Dev. 1996; 10(2):129-41. DOI: 10.1101/gad.10.2.129. View

14.

Schneider B, Yang Q, Futcher A . Linkage of replication to start by the Cdk inhibitor Sic1. Science. 1996; 272(5261):560-2. DOI: 10.1126/science.272.5261.560. View

15.

Bai C, Sen P, Hofmann K, Ma L, Goebl M, Harper J . SKP1 connects cell cycle regulators to the ubiquitin proteolysis machinery through a novel motif, the F-box. Cell. 1996; 86(2):263-74. DOI: 10.1016/s0092-8674(00)80098-7. View

16.

Hershko A, Heller H . Occurrence of a polyubiquitin structure in ubiquitin-protein conjugates. Biochem Biophys Res Commun. 1985; 128(3):1079-86. DOI: 10.1016/0006-291x(85)91050-2. View

17.

Evan G, LEWIS G, Ramsay G, Bishop J . Isolation of monoclonal antibodies specific for human c-myc proto-oncogene product. Mol Cell Biol. 1985; 5(12):3610-6. PMC: 369192. DOI: 10.1128/mcb.5.12.3610-3616.1985. View

18.

Mendenhall M, Jones C, Reed S . Dual regulation of the yeast CDC28-p40 protein kinase complex: cell cycle, pheromone, and nutrient limitation effects. Cell. 1987; 50(6):927-35. DOI: 10.1016/0092-8674(87)90519-8. View

19.

Goebl M, Yochem J, Jentsch S, McGrath J, Varshavsky A, Byers B . The yeast cell cycle gene CDC34 encodes a ubiquitin-conjugating enzyme. Science. 1988; 241(4871):1331-5. DOI: 10.1126/science.2842867. View

20.

Chau V, Tobias J, Bachmair A, Marriott D, Ecker D, Gonda D . A multiubiquitin chain is confined to specific lysine in a targeted short-lived protein. Science. 1989; 243(4898):1576-83. DOI: 10.1126/science.2538923. View