Cyclin-dependent kinase 619200 220770552 2008-06-21T14:19:59Z DOI bot 6652755 Citation maintenance. You can [[WP:DOI|use this bot]] yourself! Please [[User:DOI_bot/bugs|report any bugs]]. [[image:Cell Cycle 2.png|thumb|350px|Schematic of the cell cycle. outer ring: I=[[Interphase]], M=[[Mitosis]]; inner ring: M=Mitosis; G1=[[G1 phase|Growth phase 1]]; S=[[S phase|Synthesis]]; G2=[[G2 phase|Growth phase 2]]. The duration of mitosis in relation to the other phases has been exaggerated in this diagram]] '''Cyclin-dependent kinases''' ('''CDK''') belong to a group of [[protein kinase]]s originally discovered as being involved in the regulation of the [[cell cycle]]. CDK9, however, is an exception, as it plays no role in cell cycle regulation. CDKs are also involved in the regulation of [[Transcription (genetics)|transcription]] and [[mRNA]] processing. CDKs phosphorylate proteins on [[serine]] and [[threonine]] [[amino acid|amino acid residues]]: they are [[serine/threonine kinases]]. A cyclin-dependent kinase is activated by association with a [[cyclin]], forming a [[cyclin-dependent kinase complex]]. ==Types== '''A list of CDKs with their regulator protein, cyclin or other.''' *[[CDK1]]; [[cyclin A]], [[cyclin B]] *[[CDK2]]; [[cyclin A]], [[cyclin E]] *{{Gene|CDK3}} *[[CDK4]]; [[cyclin D1]], [[cyclin D2]], [[cyclin D3]] *[[CDK5]]; p35 ([http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=603460 p35 would be another type of regulator that looks only marginally similar to cyclins]). See also [[CDKL5]]. *[[CDK6]]; [[cyclin D1]], [[cyclin D2]], [[cyclin D3]] *[[CDK7]]; [[cyclin H]] *{{Gene|CDK8}}; [[cyclin C]] *[[CDK9]]; [[cyclin T1]], [[cyclin T2a]], [[cyclin T2b]], [[cyclin K ]] *{{Gene|CDK10}} * CDK11 ({{Gene|CDC2L2}}) ; [[cyclin L]] ==Regulation== A cyclin-CDK complex can be regulated by several [[kinase]]s and [[phosphatase]]s, including [[Wee (kinase)|Wee]], and [[CDK-activating kinase]] (CAK), and [[Cdc25 (phosphatase)|Cdc25]]. CAK adds an activating phosphate to the complex, while Wee adds an inhibitory phosphate; the presence of both activating and inhibitory phosphates renders the complex inactive. Cdc25 is a phosphatase that removes the inhibitor phosphate added by Wee, rendering the complex active. Cdk [[feedback|feeds back]] on Wee and Cdc25 to inhibit and enhance their respective activities. == Cyclin and Cdk used in Cell Cycle == {| class="wikitable" |- ! Phase ! Cyclin ! Cdk |- | G1 | D, E | CDK4, CDK2, CDK6 |- | S | A, E | CDK2 |- | G2 | A | CDK2 |- | M | B | CDK1 |} ==History== [[Leland H. Hartwell]], [[R. Timothy Hunt]], and [[Paul M. Nurse]] won the 2001 [[Nobel Prize in Physiology or Medicine]] for their complete description of [[cyclin]] and cyclin-dependent kinase mechanisms, central molecules in the regulation of the cell cycle. ==Medical significance== CDKs are considered a potential target for anti-cancer medication. If it is possible to selectively interrupt the cell cycle regulation in cancer cells by interfering with CDK action, the cell will die. Currently, some CDK inhibitors such as [[Seliciclib]] are undergoing clinical trials. Although it was originally developed as a potential anti-cancer drug, in recent laboratory tests Seliciclib has also proven to induce [[apoptosis]] in [[neutrophil granulocytes]] which mediate [[inflammation]].<ref>Rossi, Adriano G.; Sawatzky, Deborah A.; Walker, Annemieke; Ward, Carol; Sheldrake, Tara A.; Riley, Nicola A.; Caldicott, Alison; Martinez-Losa, Magdalena; Walker, Trevor R.; Duffin, Roger; Gray, Mohini; Crescenzi, Elvira; Martin, Morag C.; Brady, Hugh J; Savill, John S.; Dransfield, Ian & Haslett, Christopher (2006): Cyclin-dependent kinase inhibitors enhance the resolution of inflammation by promoting inflammatory cell apoptosis. ''Nature Medicine'' '''12''' (in print). {{DOI|10.1038/nm1468}}</ref> This means that novel drugs for treatment of [[chronic]] inflammation diseases such as [[arthritis]] or [[cystic fibrosis]] could be developed. More research is required, however, because disruption of the CDK-mediated pathway has potentially serious consequences; while CDK inhibitors seem promising, it has to be determined how side effects can be limited so that only target cells are affected. As such diseases are currently treated with [[glucocorticoid]]s, which have often serious side effects, even a minor success would mean an improvement. == References == <references/> ==External links== * {{MeshName|Cyclin-Dependent+Kinases}} * {{EC number|2.7.11.22}} *[http://www.genome.ad.jp/kegg/pathway/hsa/hsa04110.html KEGG - Human Cell Cycle] * {{cite journal |author=Loyer P, Trembley J, Katona R, Kidd V, Lahti J |title=Role of CDK/cyclin complexes in transcription and RNA splicing |journal=Cell Signal |volume=17 |issue=9 |pages=1033–51 |year=2005 |pmid=15935619 |doi=10.1016/j.cellsig.2005.02.005}} [[Category:Cell cycle]] [[Category:Proteins]] {{Serine/threonine-specific protein kinases}} {{Cell cycle proteins}} [[de:Cyclin-abhängige Kinase]] [[es:Kinasa dependiente de ciclina]] [[hu:Ciklin-dependens kináz]] [[fi:Sykliineistä riippuvaiset kinaasit]]