UNASSIGNED: Mediator is a conserved multi-subunit signal processor through which regulatory informatiosn conveyed by gene-specific transcription factors is transduced to RNA Polymerase II (Pol II). In @entity1 , @entity25612 , @entity6530 , @entity41183 and @entity60376 ( @entity60376 ) comprise a four-subunit "kinase" module that exists in variable association with a 26-subunit Mediator core. Genetic and biochemical studies have established the Mediator kinase module as a major ingress of developmental and oncogenic signaling through Mediator, and much of its function in signal-dependent gene regulation derives from its resident @entity41183 kinase activity. For example, @entity41183 -targeted substrate phosphorylation impacts transcription factor half-life, Pol II activity and chromatin chemistry and functional status. Recent structural and biochemical studies have revealed a precise network of physical and functional subunit interactions required for proper kinase module activity. Accordingly, pathologic change in this activity through altered expression or mutation of constituent kinase module subunits can have profound consequences for altered signaling and @entity5 formation. Herein, we review the structural organization, biological function and oncogenic potential of the Mediator kinase module. We focus principally on @entity5 -associated alterations in kinase module subunits for which mechanistic relationships as opposed to strictly correlative associations are established. These considerations point to an emerging picture of the Mediator kinase module as an oncogenic unit, one in which pathogenic activation/deactivation through component change drives @entity5 formation through perturbation of signal-dependent gene regulation. It follows that therapeutic strategies to combat @entity41183 -driven @entity5 will involve targeted modulation of @entity41183 activity or pharmacologic manipulation of dysregulated @entity41183 -dependent signaling pathways.

Mediator kinase module and XXXX tumorigenesis.

@entity1 :: ('9606', 'Species') :: ['humans'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor', 'tumors'] @entity25612 :: ('9969', 'Gene') :: ['MED13'] @entity41183 :: ('1024', 'Gene') :: ['CDK8'] @entity60376 :: ('892', 'Gene') :: ['CycC', 'Cyclin C'] @entity6530 :: ('9968', 'Gene') :: ['MED12']
@entity1 :: (9606,Species) :: ['human']
