Sandbox Reserved 826: Difference between revisions
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== '''Introduction'''== | == '''Introduction'''== | ||
Cyclin dependent kinasaes (CDKs) are a family of serine/threonine kinases, which are responsible for cell cycle progression. They are regulated by several upstream pathways, such as the CDK activating kinase and interaction with Cyclin D. After association of CDK with cyclin, the active CDK/cyclin complex phosphorylates and herefore inactivates [http://www.proteopedia.org/wiki/index.php/Retinoblastoma_protein retinoblastoma] protein family members. This leads to activation of E2F target genes. One of these genes is cyclin E which triggers G1 phase cell cycle progression.<br /> | Cyclin dependent kinasaes (CDKs) are a family of serine/threonine kinases, which are responsible for cell cycle progression. They are regulated by several upstream pathways, such as the CDK activating kinase and interaction with Cyclin D. After association of CDK with cyclin, the active CDK/cyclin complex phosphorylates and herefore inactivates [http://www.proteopedia.org/wiki/index.php/Retinoblastoma_protein retinoblastoma] protein family members. This leads to activation of E2F target genes. One of these genes is cyclin E which triggers G1 phase cell cycle progression.<br /> | ||
CDKs and cyclins are particularly interesting because a dysfunction of their pathways are associated to numerous cancers. Among all genetic alterations of CDK/cyclin in cancer that one of CDK4 and cyclin D1 is most common. Appearance of breast cancer goes normally hand in hand with increased cyclin D1 levels, caused by genetic amplification or overexpression <ref> PMID: 15961768 </ref>. In liposarcomas the CDK4 gene is amplified <ref> PMID: 16160477 </ref>. Cyclin D1 translocations play also a role in mantle cell lymphoma and multiple myelomas <ref> PMID: 12683869 </ref>. Furthermore mutations of CDK4, which alter its structure in a manner that it becomes unable to bind regulative tumor supressor proteins result in defective CDK4 repression and therefore dysregulate the cell | CDKs and cyclins are particularly interesting because a dysfunction of their pathways are associated to numerous cancers. Among all genetic alterations of CDK/cyclin in cancer that one of CDK4 and cyclin D1 is most common. Appearance of breast cancer goes normally hand in hand with increased cyclin D1 levels, caused by genetic amplification or overexpression <ref> PMID: 15961768 </ref>. In liposarcomas the CDK4 gene is amplified <ref> PMID: 16160477 </ref>. Cyclin D1 translocations play also a role in mantle cell lymphoma and multiple myelomas <ref> PMID: 12683869 </ref>. Furthermore mutations of CDK4, which alter its structure in a manner that it becomes unable to bind regulative tumor supressor proteins result in defective CDK4 repression and therefore dysregulate the cell cycle. It becomes obvious that cyclin D1 CDK4 interaction is critical for the development of several cancers. Therefore CDKs, in particular CDK4 are a promising target of novel cancer drugs. | ||
== '''CDK4 structure''' == | == '''CDK4 structure''' == | ||
