Cyclin - Function

Function

Cyclins were originally named because their concentration varies in a cyclical fashion during the cell cycle. (Note that the cyclins are now classified according to their conserved cyclin box structure, and not all these cyclins alter in level through the cell cycle.) The oscillations of the cyclins, namely fluctuations in cyclin gene expression and destruction by the ubiquitin mediated proteasome pathway, induce oscillations in Cdk activity to drive the cell cycle. A cyclin forms a complex with Cdk, which begins to activate the Cdk, but the complete activation requires phosphorylation, as well. Complex formation results in activation of the Cdk active site. Cyclins themselves have no enzymatic activity but have binding sites for some substrates and target the Cdks to specific subcellular locations.

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

In an interview for the BBC4 documentary "The Life Scientific" (aired on 13/12/2011) hosted by Jim Al-Khalili, R. Timothy Hunt explained that the name "cyclin" was originally named after his hobby cycling. It was only after the naming did its importance in the cell cycle become apparent. As it was appropriate the name stuck. R.Timothy Hunt: "By the way the name cyclin, which I coined, was really a joke, it's because I like cycling so much at the time but they did come and go in the cell..."

Cyclins, when bound with the dependent kinases, such as the p34 (cdc2) or cdk1 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. Cyclins can be divided into four classes based on their behavior in the cell cycle of vertebrate somatic cells and yeast cells: G1/S cyclins, S cyclins, M cyclins, G1 cyclins. This division is useful when talking about most cell cycles, but it is not universal as some cyclins have different functions or timing in different cell types.

G1/S Cyclins rise in late G1 and fall in early S phase. The Cdk- G1/S cyclin complex begins to induce the initial processes of DNA replication, primarily by arresting systems that prevent S phase Cdk activity in G1. The cyclins also promote other activities to progress the cell cycle, like centrosome duplication in vertebrates or spindle pole body in yeast. The rise in presence of G1/S cyclins is paralleled by a rise in S cyclins.

S cyclins bind to Cdk and the complex directly induces DNA replication. The levels of S cyclins remain high, not only throughout S phase, but through G2 and early mitosis as well to promote early events in mitosis.

M cyclin concentrations rise as the cell begins to enter mitosis and the concentrations peak at metaphase. Cell changes in the cell cycle like the assembly of mitotic spindles and alignment of sister-chromatids along the spindles are induced by M cyclin- Cdk complexes. The destruction of M cyclins during metaphase and anaphase, after the Spindle Assembly Checkpoint is satisfied, causes the exit of mitosis and cytokinesis.

G1 cyclins do not behave like the other cyclins, in that the concentrations increase gradually (with no oscillation), throughout the cell cycle based on cell growth and the external growth-regulatory signals. The presence of G cyclins coordinate cell growth with the entry to a new cell cycle.

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