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CCNs

Monday 14 July 2003

Cyclins (CCNs) are a family of proteins involved in the progression of cells through the cell cycle.

A cyclin (CCN) forms a complex with the cyclin-dependent kinase (CDKs), which activates the latter’s 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, cyclin detaches from CDK, inhibiting the enzyme’s activity, probably by causing a protein chain to block the enzymatic site.

There are several different cyclins which are active in different parts of the cell cycle and which cause the Cdk to phosphorylate different substrates.

However, there are several "orphan" cyclins which no Cdk partner has been identified. For example, cyclin F is one of orphan cyclin that is essential for G2/M transition.

One major cyclin is cyclin B (CCNBs), a mitotic cyclin. The amount of cyclin B (which binds to Cdk1) and the activity of the cyclin B-Cdk complex rise through the cell cycle until mitosis, when they fall abruptly due to degradation. The complex of Cdk and cyclin B is called maturation promoting factor (MPF).

Other cyclins include cyclin E (CCNEs) (binds to G1 phase Cdk), which is required for the transition from G1 to S phase and cyclin A (binds to S phase Cdk2) and is required for the cell to progress through the S phase.

Members

CCNA1 CCNA2 CCNB1 CCNB2 CCNB3 CCNC CCND1 CCND2 CCND3
CCNE1 CCNE2 CCNF CCNG1 CCNG2 CCNH

Types

G(1) cyclins CCND1 CCND2 CCND3 CCNE1 CCNE2

Pathology

- A new subtype of bone sarcoma is defined by BCOR-CCNB3 gene fusion. (22387997)

  • CCNB3 immunohistochemistry is a powerful diagnostic marker for this subgroup of sarcoma and that overexpression of BCOR-CCNB3 or of truncated CCNB3 activates S phase in NIH3T3 cells.
  • The intrachromosomal X-chromosome fusion represents a new subtype of bone sarcoma caused by a newly identified gene fusion mechanism.

References

- A new subtype of bone sarcoma defined by BCOR-CCNB3 gene fusion. Pierron G, Tirode F, Lucchesi C, Reynaud S, Ballet S, Cohen-Gogo S, Perrin V, Coindre JM, Delattre O. Nat Genet. 2012 Mar 4. PMID: 22387997v

Reviews

- Bloom J, Cross FR. Multiple levels of cyclin specificity in cell-cycle control. Nat Rev Mol Cell Biol. 2007 Feb;8(2):149-60. PMID: 17245415

- Bai C, Richman R, Elledge SJ. (1994) Human cyclin F. EMBO Journal. 13(24):6087-98.

- Kong M, Barnes EA, Ollendorff V, Donoghue DJ. (2000) Cyclin F regulates the nuclear localization of cyclin B1 through a cyclin-cyclin interaction. EMBO Journal. 19(6):1378-88.

- Fung, T. K. and Poon R.Y.C. (2005). A roller coaster ride with the mitotic cyclins. Seminars in Cell & Developmental Biology. 16 (3):335-342.