Mediator complex subunit 4 (MED4)

Mediator complex subunit 4 (MED4) is a protein component of the multiprotein Mediator complex, which functions as a transcriptional coactivator essential for the regulated transcription of virtually all RNA polymerase II-dependent genes. MED4 acts as a bridge linking gene-specific regulatory transcription factors to the basal transcription machinery, facilitating assembly of the preinitiation complex with RNA polymerase II and general transcription factors. MED4 participates in activation of nuclear receptors, such as the vitamin D receptor, as part of the DRIP (vitamin D receptor-interacting protein) complex. In cancer biology, particularly retinoblastoma, MED4 is essential for cell survival when both RB1 alleles are inactivated, making it a synthetic lethal partner and a potential therapeutic vulnerability in tumors lacking RB1. Alternative splicing results in multiple isoforms of MED4.

Other names

TRAP36VDRIPHSPC126ARC36DRIP36Activator-recruited cofactor 36 kDa componentVitamin D3 receptor-interacting protein complex 36 kDa componentTRAP/SMCC/PC2 subunit p36 subunitFLJ10956RP11-90M2.2

Not applicable for direct drug targeting; if therapeutically targeted, synthetic lethality in RB1-null environments could be harnessed