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Dysregulation of CDK8 and Cyclin C in tumorigenesis.
J Genet Genomics. 2011 Oct 20; 38(10):439-52.JG

Abstract

Appropriately controlled gene expression is fundamental for normal growth and survival of all living organisms. In eukaryotes, the transcription of protein-coding mRNAs is dependent on RNA polymerase II (Pol II). The multi-subunit transcription cofactor Mediator complex is proposed to regulate most, if not all, of the Pol II-dependent transcription. Here we focus our discussion on two subunits of the Mediator complex, cyclin-dependent kinase 8 (CDK8) and its regulatory partner Cyclin C (CycC), because they are either mutated or amplified in a variety of human cancers. CDK8 functions as an oncoprotein in melanoma and colorectal cancers, thus there are considerable interests in developing drugs specifically targeting the CDK8 kinase activity. However, to evaluate the feasibility of targeting CDK8 for cancer therapy and to understand how their dysregulation contributes to tumorigenesis, it is essential to elucidate the in vivo function and regulation of CDK8-CycC, which are still poorly understood in multi-cellular organisms. We summarize the evidence linking their dysregulation to various cancers and present our bioinformatics and computational analyses on the structure and evolution of CDK8. We also discuss the implications of these observations in tumorigenesis. Because most of the Mediator subunits, including CDK8 and CycC, are highly conserved during eukaryotic evolution, we expect that investigations using model organisms such as Drosophila will provide important insights into the function and regulation of CDK8 and CycC in different cellular and developmental contexts.

Authors+Show Affiliations

Department of Chemistry, University of Louisiana at Lafayette, USA.No affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

22035865

Citation

Xu, Wu, and Jun-Yuan Ji. "Dysregulation of CDK8 and Cyclin C in Tumorigenesis." Journal of Genetics and Genomics = Yi Chuan Xue Bao, vol. 38, no. 10, 2011, pp. 439-52.
Xu W, Ji JY. Dysregulation of CDK8 and Cyclin C in tumorigenesis. J Genet Genomics. 2011;38(10):439-52.
Xu, W., & Ji, J. Y. (2011). Dysregulation of CDK8 and Cyclin C in tumorigenesis. Journal of Genetics and Genomics = Yi Chuan Xue Bao, 38(10), 439-52. https://doi.org/10.1016/j.jgg.2011.09.002
Xu W, Ji JY. Dysregulation of CDK8 and Cyclin C in Tumorigenesis. J Genet Genomics. 2011 Oct 20;38(10):439-52. PubMed PMID: 22035865.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dysregulation of CDK8 and Cyclin C in tumorigenesis. AU - Xu,Wu, AU - Ji,Jun-Yuan, Y1 - 2011/09/16/ PY - 2011/07/25/received PY - 2011/09/05/revised PY - 2011/09/06/accepted PY - 2011/11/1/entrez PY - 2011/11/1/pubmed PY - 2012/2/24/medline SP - 439 EP - 52 JF - Journal of genetics and genomics = Yi chuan xue bao JO - J Genet Genomics VL - 38 IS - 10 N2 - Appropriately controlled gene expression is fundamental for normal growth and survival of all living organisms. In eukaryotes, the transcription of protein-coding mRNAs is dependent on RNA polymerase II (Pol II). The multi-subunit transcription cofactor Mediator complex is proposed to regulate most, if not all, of the Pol II-dependent transcription. Here we focus our discussion on two subunits of the Mediator complex, cyclin-dependent kinase 8 (CDK8) and its regulatory partner Cyclin C (CycC), because they are either mutated or amplified in a variety of human cancers. CDK8 functions as an oncoprotein in melanoma and colorectal cancers, thus there are considerable interests in developing drugs specifically targeting the CDK8 kinase activity. However, to evaluate the feasibility of targeting CDK8 for cancer therapy and to understand how their dysregulation contributes to tumorigenesis, it is essential to elucidate the in vivo function and regulation of CDK8-CycC, which are still poorly understood in multi-cellular organisms. We summarize the evidence linking their dysregulation to various cancers and present our bioinformatics and computational analyses on the structure and evolution of CDK8. We also discuss the implications of these observations in tumorigenesis. Because most of the Mediator subunits, including CDK8 and CycC, are highly conserved during eukaryotic evolution, we expect that investigations using model organisms such as Drosophila will provide important insights into the function and regulation of CDK8 and CycC in different cellular and developmental contexts. SN - 1673-8527 UR - https://www.unboundmedicine.com/medline/citation/22035865/Dysregulation_of_CDK8_and_Cyclin_C_in_tumorigenesis_ DB - PRIME DP - Unbound Medicine ER -