Cyclin

Cyclins were originally discovered by R. Timothy Hunt in 1982 while studying the cell cycle of sea urchins. In an interview hosted by Jim Al-Khalili and R. Timothy Hunt for "The Life Scientific", which aired on December 13, 2011, 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 liked cycling so much at the time, but they did come and go in the cell..." == 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, 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. Expression of cyclins detected immunocytochemically in individual cells in relation to cellular DNA content (cell cycle phase), or in relation to initiation and termination of DNA replication during S-phase, can be measured by flow cytometry. Kaposi sarcoma herpesvirus (KSHV) encodes a D-type cyclin (ORF72) that binds CDK6 and is likely to contribute to KSHV-related cancers. == Domain structure ==

Cyclins are generally very different from each other in primary structure, or amino acid sequence. However, all members of the cyclin family are similar in 100 amino acids that make up the cyclin box. Cyclins contain two domains of a similar all-α fold, the first located at the N-terminus and the second at the C-terminus. All cyclins are believed to contain a similar tertiary structure of two compact domains of 5 α helices. The first of which is the conserved cyclin box, outside of which cyclins are divergent. For example, the amino-terminal regions of S and M cyclins contain short destruction-box motifs that target these proteins for proteolysis in mitosis. == Types ==

There are several different cyclins that are active in different parts of the cell cycle and that 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. A study in C. elegans revealed the specific roles of mitotic cyclins. Notably, recent studies have shown that cyclin A creates a cellular environment that promotes microtubule detachment from kinetochores in prometaphase to ensure efficient error correction and faithful chromosome segregation. Cells must separate their chromosomes precisely, an event that relies on the bi-oriented attachment of chromosomes to spindle microtubules through specialized structures called kinetochores. In the early phases of division, there are numerous errors in how kinetochores bind to spindle microtubules. The unstable attachments promote the correction of errors by causing a constant detachment, realignment and reattachment of microtubules from kinetochores in the cells as they try to find the correct attachment. Protein cyclin A governs this process by keeping the process going until the errors are eliminated. In normal cells, persistent cyclin A expression prevents the stabilization of microtubules bound to kinetochores even in cells with aligned chromosomes. As levels of cyclin A decline, microtubule attachments become stable, allowing the chromosomes to be divided correctly as cell division proceeds. In contrast, in cyclin A-deficient cells, microtubule attachments are prematurely stabilized. Consequently, these cells may fail to correct errors, leading to higher rates of chromosome mis-segregation. 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 S 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 G2 to M phase. Subtypes The specific cyclin subtypes along with their corresponding CDK (in brackets) are: ==Other proteins containing this domain==

In addition, the following human protein contains a cyclin domain: CNTD1 == 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. == References ==