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Cyclin, N-terminal domain
Identifiers
Symbol Cyclin_N
Pfam PF00134
InterPro IPR006671
PROSITE PDOC00264
SCOP 1vin
Cyclin, C-terminal domain
Identifiers
Symbol Cyclin_C
Pfam PF02984
InterPro IPR004367

Cyclins are a family of proteins which control the progression of cells through the cell cycle by activating cyclin-dependent kinase (Cdk) enzymes.[1]

Contents

Function

Expression of human cyclins through the cell cycle.

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. They were discovered by R. Timothy Hunt in 1982 while studying the cell cycle of sea urchins[2].

A cyclin forms a complex with Cdk. Complex formation results in activation of the Cdk active site.

When concentrations in the cell are low, cyclins dissociate from Cdk, thus inhibiting enzymatic activity; this probably occurs due to a protein chain of the Cdk blocking the active site upon cyclin dissocation.[3][4] Cyclins themselves have no enzymatic activity.

Cyclins, when bound with the dependent kinases, such as the p34 (cdc2) or cdk2 proteins, form the maturation promoting factor. MPFs activate other proteins through phosphorylation. These phosphorylated proteins in turn are responsible for specific events during cycle division such as microtubule formation and chromatin remodeling.

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.[5][6]

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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,
  • 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 G2 to M phase.

Subtypes

Specific cyclin subtypes include:

family members
A CCNA1, CCNA2
B CCNB1, CCNB2, CCNB3
C CCNC
D CCND1, CCND2, CCND3
E CCNE1, CCNE2
F CCNF
G CCNG1, CCNG2
H CCNH
I CCNI, CCNI2
J CCNJ, CCNJL
K CCNK
L CCNL1, CCNL2
O CCNO
T CCNT1, CCNT2
Y CCNY, CCNYL1, CCNYL2, CCNYL3

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.[7]

References

  1. ^ Galderisi U, Jori FP, Giordano A (August 2003). "Cell cycle regulation and neural differentiation". Oncogene 22 (33): 5208–19. doi:10.1038/sj.onc.1206558. PMID 12910258.  
  2. ^ http://nobelprize.org/nobel_prizes/medicine/laureates/2001/hunt-autobio.html
  3. ^ Bai C, Richman R, Elledge SJ (1994). "Human cyclin F". EMBO J. 13 (24): 6087–98. PMID 7813445.  
  4. ^ Kong M, Barnes EA, Ollendorff V, Donoghue DJ (2000). "Cyclin F regulates the nuclear localization of cyclin B1 through a cyclin-cyclin interaction". EMBO J. 19 (6): 1378–88. doi:10.1093/emboj/19.6.1378. PMID 10716937.  
  5. ^ Fung TK, Poon RY (2005). "A roller coaster ride with the mitotic cyclins". Semin. Cell Dev. Biol. 16 (3): 335–42. doi:10.1016/j.semcdb.2005.02.014. PMID 15840442.  
  6. ^ Gerald Karp, (2007). Cell and Molecular Biology: Concepts and Experiments. New York: Wiley. pp. 148, 165–170, and 624–664. ISBN 0-470-04217-6.  
  7. ^ "The Nobel Prize in Physiology or Medicine 2001". The Nobel Foundation. http://nobelprize.org/nobel_prizes/medicine/laureates/2001/index.html. Retrieved 2009-03-15.  

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


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