The Mediator complex is an important component of the eukaryotic transcriptional machinery. As an essential link between transcription factors and RNA polymerase II, the Mediator complex transduces diverse signals to ...The Mediator complex is an important component of the eukaryotic transcriptional machinery. As an essential link between transcription factors and RNA polymerase II, the Mediator complex transduces diverse signals to genes involved in different pathways. The plant Mediator complex was recently purified and comprises conserved and specific subunits. It functions in concert with transcription factors to modulate various responses. In this review, we summarize the recent advances in understanding the plant Mediator complex and its diverse roles in plant growth, development, defense, non-coding RNA production, response to abiotic stresses, flowering, genomic stability and metabolic homeostasis. In addition, the transcription factors interacting with the Mediator complex are also highlighted.展开更多
Appropriately controlled gene expression is fundamental for normal growth and survival of all living organisms. In eukaryotes, the tran- scription of protein-coding mRNAs is dependent on RNA polymerase II （Pol II）. ...Appropriately controlled gene expression is fundamental for normal growth and survival of all living organisms. In eukaryotes, the tran- scription 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 CDKS-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.展开更多
文摘The Mediator complex is an important component of the eukaryotic transcriptional machinery. As an essential link between transcription factors and RNA polymerase II, the Mediator complex transduces diverse signals to genes involved in different pathways. The plant Mediator complex was recently purified and comprises conserved and specific subunits. It functions in concert with transcription factors to modulate various responses. In this review, we summarize the recent advances in understanding the plant Mediator complex and its diverse roles in plant growth, development, defense, non-coding RNA production, response to abiotic stresses, flowering, genomic stability and metabolic homeostasis. In addition, the transcription factors interacting with the Mediator complex are also highlighted.
基金supported by grants from National Institutes of Health(DK093623)American Diabetes Association(7-11-BS-173)Einstein Diabetes Research Center(P60-DK020541)~~
基金supported by a sub-award of the NIH LEQSF-INBRE grant(P20RR016456) to WXa grant from the American Heart Association(11SDG7590123) to JYJ
文摘Appropriately controlled gene expression is fundamental for normal growth and survival of all living organisms. In eukaryotes, the tran- scription 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 CDKS-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.
