Cell Cycle: Regulation by Cyclins

Andrew W Truman, University of Chicago, Chicago, Illinois, USA
Ana A Kitazono, Universidad Agraria La Molina, Lima, Peru, Peru
Jonathan N Fitz Gerald, Rhodes College, Memphis, TN, USA
Stephen J Kron, University of Chicago, Chicago, Illinois, USA

Published online: May 2012

DOI: 10.1002/9780470015902.a0001364.pub3

The cell cycle is defined as the periodic occurrence of events that result in chromosome duplication (deoxyribonucleic acid, DNA replication in S phase) and separation (mitosis). This process is directly regulated by both external stimuli (such as nutrient availability) and internal stimuli (such as cell size and DNA integrity). These events are co‐ordinately driven by the cyclin‐dependent kinases (CDKs). Although the expression of CDKs typically remains relatively constant, their activities are highly regulated by CDK‐binding proteins known as Cyclins. Cyclins are structurally related proteins whose levels fluctuate throughout the cell cycle. Cyclin levels in the cell are dynamically regulated through tight control over both their rate of synthesis and degradation via ubiquitin‐mediated proteolysis. These CDK activators also impart distinct substrate specificity to CDKs for the temporal regulation of cell division.

Key Concepts:

  • Cyclin levels oscillate throughout the cell cycle.
  • Cyclins bind to CDKs and regulate their kinase activity.
  • Cyclin‐CDK complexes direct the specificity of appropriate substrate interactions during the cell cycle.
  • Inappropriate regulation of cyclins can be both the cause and the result of oncogenesis.
  • As well as controlling normal cell cycle progression, cyclins function also in the exiting of the cell cycle (such as G0 in terminally differentiated cells and the onset of senescence caused by DNA damage).

Keywords: cyclin; CDK; cell cycle; CKI; cancer; senescence; substrate specificity

Figure 1. Cyclin expression and degradation in the yeast and mammalian (human) cell cycle. The combination of both protein level and activity are depicted in the figure. D cyclin expression is induced by mitogenic signals and can be found in the cell during two successive cell cycles under the constant presence of the signal. However, the main role of D cyclins is at the G1/S transition.
Figure 2. Cyclin B and Cdk1 protein modifications during M and interphase (I). Cdk1 is phosphorylated after binding with cyclin B and the complex is fully activated by dephosphorylation at the Thr14 and Tyr15 residues, resulting in the onset of mitosis. During anaphase, cyclin B is targeted for proteasome‐dependent degradation by the APC, an ubiquitin‐protein ligating enzyme.
Figure 3. Conservation of the ‘cyclin‐box fold’ among cyclin A, the retinoblastoma protein and the transcription factor TFIIB.
Figure 4. Structural transformations in CDK during activation and inhibition. CDKs (blue), by themselves, are inactive. Activation occurs through phosphorylation of the T loop (green) and the binding of cyclin (purple) at the PSTAIRE helix (red). These events lead to a conformational change that produces a functional active site (yellow, see text for details). Tertiary inhibitors of the CIP/KIP1 family (p27; orange) block kinase activity by disrupting the N‐terminal domain and penetrating into the catalytic site. Binary inhibitors of the INK family (p19; salmon) distort the CDK N‐terminal domain.
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Intracellular and Extracellular Signalling | Cell Cycle
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Article Title: Cell Cycle: Regulation by Cyclins
 
How to Cite close
Truman, Andrew W, Kitazono, Ana A, Fitz Gerald, Jonathan N, and Kron, Stephen J(May 2012) Cell Cycle: Regulation by Cyclins. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0001364.pub3]