cyclin

This article may be confusing or unclear to readers. Please help clarify the article; suggestions may be found on the talk page. (March 2009)

Cyclins are a family of proteins which control the progression of cells through the cell cycle by regulation of cyclin-dependent kinases (CDKs).^[1] Cyclins themselves have no enzymatic activity.

The individual steps of cell division must carefully be controlled to make sure that all the required molecular components are ready before proceeding to the next step. This control ensures an orderly division of the cell with high fidelity DNA replication. This control includes checking for DNA damage which if present would be propagated during cell division with often catastrophic consequences for the cell progeny. If DNA damage is present, the cell cycle must be paused in order to allow time for DNA repair before proceeding with cell division.

Cyclins are a critical component of this cell cycle control mechanism. Cyclins, together with the p34 (cdc2) or cdk2 kinases, form the Maturation Promoting Factor (MPF). MPFs activate other proteins through phosphorylation. These phosphorylated proteins in turn are responsible for specific events during cycle division such as microtubule formation, chromatin remodeling, etc.

Function

Expression of human cyclins through the cell cycle.

A cyclin forms a complex with its partner cyclin-dependent kinase (Cdk). Complex formation results in activation of the Cdk protein kinase function.

Cyclins are so named because their concentration varies in a cyclical fashion during the cell cycle; they are produced or degraded as needed in order to drive the cell through the different stages of the cell cycle.

When its concentrations in the cell are low, the cyclin detaches from the Cdk, inhibiting the enzyme's activity, probably by causing a protein chain to block the enzymatic site.^[2][3]

Domain structure

Cyclins contain two domains of similar all-α fold, the first located at the N-terminus and the second at the C-terminus.

Types

There are several different cyclins which are active in different parts of the cell cycle and which cause the Cdk to phosphorylate different substrates. There are also several "orphan" cyclins for which no Cdk partner has been identified. For example, cyclin F is an orphan cyclin that is essential for G2/M transition.^[4][5]

Main groups

There are two main groups of cyclins:

• G1/S cyclins – essential for the control of the cell cycle at the G1/S transition,
  • Cyclin A / CDK2 – active in G1 phase.
  • Cyclin D / CDK4, Cyclin D / CDK6, and Cyclin E / CDK2 – regulates transition from G1 to S phase.
• G2/M cyclins – essential for the control of the cell cycle at the G2/M transition (mitosis). G2/M cyclins accumulate steadily during G2 and are abruptly destroyed as cells exit from mitosis (at the end of the M-phase).
  • Cyclin B / CDK1 – regulates progression from the S to G2 phase.

Subtypes

Specific cyclin subtypes include:

Other proteins containing this domain

In addition, the following human proteins contain a cyclin domain:

CABLES2, CNTD1, CNTD2

History

Leland H. Hartwell, R. Timothy Hunt, and Paul M. Nurse won the 2001 Nobel Prize in Physiology or Medicine for their discovery of cyclin and cyclin-dependent kinase, central molecules in the regulation of the cell cycle.^[6]

References

Further reading

• Monty Krieger; Matthew P Scott; Matsudaira, Paul T.; Lodish, Harvey F.; Darnell, James E.; Lawrence Zipursky; Kaiser, Chris; Arnold Berk (2004). Molecular cell biology (Fifth ed.). New York: W.H. Freeman and CO. ISBN 0-7167-4366-3. 

This article includes text from the public domain Pfam and InterPro IPR006671