CDK8 Protein, Human (sf9)

The CDK8-CCNC-MED12 protein is a crucial component of the Mediator complex, a coactivator integral to the regulation of gene transcription for nearly all RNA polymerase II-dependent genes. As part of the Mediator complex, it acts as a bridge, conveying information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. This complex is recruited to promoters through direct interactions with regulatory proteins, serving as a scaffold for the assembly of a functional pre-initiation complex with RNA polymerase II and general transcription factors. CDK8-CCNC-MED12 exerts its regulatory functions by phosphorylating the C-terminal domain (CTD) of the large subunit of RNA polymerase II, potentially inhibiting the formation of a transcription initiation complex. Furthermore, it phosphorylates CCNH, leading to the down-regulation of the TFIIH complex and subsequent transcriptional repression. Notably, CDK8-CCNC-MED12 is recruited through interaction with MAML1, contributing to the hyperphosphorylation of the intracellular domain of NOTCH and facilitating its degradation. These multifaceted roles underscore the significance of CDK8-CCNC-MED12 in orchestrating the intricate processes of gene transcription regulation.