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CDK8 is a positive regulator of transcriptional elongation within the serum response network.
Author(s) -
Espinosa Joaquin M,
Donner Aaron J,
Galbraith Matthew,
Taatjes Dylan,
Ebmeier Chris
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.456.5
Subject(s) - cyclin dependent kinase 8 , mediator , rna polymerase ii , repressor , p tefb , transcription (linguistics) , biology , microbiology and biotechnology , promoter , regulator , transcription factor ii d , transcriptional regulation , gene , transcription factor , gene expression , genetics , signal transduction , notch signaling pathway , linguistics , philosophy
The Mediator complex allows communication between transcription factors and RNA polymerase II (RNAPII). CDK8, the kinase found in some variants of Mediator, has been characterized mostly as a transcriptional repressor. Recently, CDK8 was demonstrated to be a potent oncoprotein. Interestingly, we found that CDK8 is prevalently a positive regulator of gene expression within the serum response network, as it is required for expression of several members of the AP‐1 and EGR family of oncogenic transcription factors (e.g. FOS, JUN, EGR1–3). Mechanistic studies demonstrate that CDK8 is not required for recruitment of RNAPII and promoter escape at these loci. Instead, CDK8 depletion leads to the appearance of slower elongation complexes carrying hypophosphorylated RNAPII. We determined that CDK8‐Mediator regulates precise steps in the assembly of a functional elongation complex, including the recruitment of P‐TEFb and BRD4, but is dispensable for recruitment of SPT5 and FACT. Furthermore, CDK8‐Mediator specifically interacts with P‐TEFb. Thus, we uncovered a novel role for CDK8 in transcriptional regulation that may contribute to its oncogenic effects.