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Multiple levels of cyclin specificity in cell-cycle control

Nature Reviews Molecular Cell Biology volume 8, pages 149–160 (2007)Cite this article

Key Points

  • In budding yeast, multiple cyclins activate a single cyclin-dependent kinase (Cdk) to control progression through the cell cycle.

  • The ability of specific cyclins to target Cdk to different substrates reflects the timing of expression of individual cyclins in some cases, and in others it reflects the intrinsic properties of individual cyclin proteins.

  • Mechanisms that lead to cyclin specificity include transcriptional activation, proteolysis, negative regulation by particular inhibitors, subcellular localization and binding to specific substrates.

  • Intrinsic cyclin-specific properties affect both the regulation of cyclins as well as the targeting of particular substrates to control downstream events; signal-transduction pathways have evolved to exploit cyclin specificity to produce cell-cycle-specific responses to specific signals.

  • The specificity of different cyclins is thought to be important for the proper order and timing of cell-cycle events.

Abstract

Cyclins regulate the cell cycle by binding to and activating cyclin-dependent kinases (Cdks). Phosphorylation of specific targets by cyclin–Cdk complexes sets in motion different processes that drive the cell cycle in a timely manner. In budding yeast, a single Cdk is activated by multiple cyclins. The ability of these cyclins to target specific proteins and to initiate different cell-cycle events might, in some cases, reflect the timing of the expression of the cyclins; in others, it might reflect intrinsic properties of the cyclins that render them better suited to target particular proteins.

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Figure 1: Cyclins in the budding yeast cell cycle.
Figure 2: Transcriptional regulation of cyclins.
Figure 3: Degradation and inhibition of cyclins.
Figure 4: Signalling pathways that regulate cyclins.
Figure 5: Cyclin control of DNA replication.
Figure 6: Cyclin control of mitotic spindle formation.
Figure 7: Cyclin control of exit from mitosis.

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Acknowledgements

J.B. is supported by a postdoctoral fellowship from the American Cancer Society. F.R.C. is supported by the National Institutes of Health.

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Authors and Affiliations

  1. Laboratory of Yeast Molecular Genetics, Rockefeller University, 1230 York Avenue, New York, 10021, New York, USA

    Joanna Bloom & Frederick R. Cross

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  1. Joanna Bloom
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Correspondence to Frederick R. Cross.

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Related links

Related links

DATABASES

Saccharomyces Genome Database

Cdc14

Cdc28

Clb1

Clb2

Clb3

Clb4

Clb5

Clb6

Cln1

Cln2

Cln3

Dyn1

Fkh2

Kar9

Ndd1

Sic1

Whi5

FURTHER INFORMATION

Frederick R. Cross's homepage

Glossary

Spindle pole body

(SPB). The yeast equivalent of the centrosome, which nucleates microtubules, including those that will form the spindle.

Anaphase promoting complex

(APC). A multicomponent ubiquitin ligase that targets proteins for degradation by the proteasome.

Forkhead transcription factor

A member of a protein family that consists of more than 40 members. This family belongs to the winged-helix class of DNA-binding proteins and its members are involved in diverse cellular functions, including glucose metabolism, apoptosis and cell-cycle regulation.

26S proteasome

A large multisubunit protease complex that selectively degrades intracellular proteins. Targeting to proteasomes occurs through the attachment of polyubiquitin tags.

SCF complex

A multisubunit ubiquitin ligase that contains Skp1, a member of the cullin family (Cdc53) and an F-box protein, as well as a RING-finger-containing protein (Roc1; also known as Rbx1).

F-box protein

A component of the machinery for the ubiquitin-dependent degradation of proteins. F-box proteins recognize specific substrates and, with the help of other subunits of the E3 ubiquitin ligase, deliver them to the E2 ubiquitin-conjugating enzyme.

α-factor

A peptide that is secreted by yeast cells of the α-mating type that causes cells of the a-mating type to prepare for mating by inducing arrest in G1, morphological changes and the transcription of genes involved in mating.

Spindle-assembly checkpoint

A checkpoint that monitors the correct attachment of chromosomes to spindles in the metaphase–anaphase transition. Activation of this checkpoint causes cell-cycle arrest as a result of the inhibition of the anaphase-promoting complex (APC).

Kinetochore

A multiprotein complex that assembles on centromeric DNA and mediates the attachment and movement of chromosomes along the microtubules of the mitotic spindle.

Mitotic exit network

(MEN). A signal-transduction pathway that is required for sustained Cdc14 release during anaphase. This allows for the degradation of mitotic cyclins and the accumulation of the Clb–Cdc28 inhibitor Sic1.

Bfa1–Bub2 GTPase-activating complex

A complex that localizes to spindle pole bodies and inhibits the activation of the mitotic exit network until the mitotic spindle is properly aligned along the mother–bud axis.

Septin ring

A complex of seven septin proteins that forms a ring at the incipient bud site before bud emergence. The septin ring determines bud-site selection and serves as a scaffold for proteins, including those involved in cell polarity, cell-wall synthesis and cytokinesis.

Origin recognition complex

(ORC). A six-subunit complex that associates with replication origins throughout the cell cycle and recruits additional replication factors to initiate DNA replication.

Minichromosome maintenance (Mcm) proteins

Six minichromosome maintenance (Mcm) proteins form a complex that binds DNA at origins of replication and helps unwind DNA to initiate replication.

RXL motif

A protein sequence in Cdc28 substrates that mediates the interaction with the hydrophobic patch of cyclins.

Cdc14 early anaphase release (FEAR) network

A signal-transduction pathway that promotes the transient release of Cdc14 from the nucleolus during early anaphase. This allows for stabilization of the mitotic spindle, segregation of ribosomal DNA and activation of the mitotic exit network.

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Bloom, J., Cross, F. Multiple levels of cyclin specificity in cell-cycle control. Nat Rev Mol Cell Biol 8, 149–160 (2007). https://doi.org/10.1038/nrm2105

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