Corepressors are coregulators that interact with transcriptional silencers in a variety of pathways such as cell proliferation, differentiation and apoptosis. Abnormal corepressor-silencer interactions have been implicated in a variety of human disease pathways including several types of leukemia. The regulation of the SMRT corepressor via the p38 and Mek-1 Kinase pathway is shown in this diagram. The EFG receptor represents one mechanism by which SMRT function is inhibited by the tyrosine kinase signaling pathway. The MEKK1 and p38 pathways are activated by EGF resulting in cross-regulation of SMRT. The induction of SMRT phosphorylation by each pathway is shown, causing SMRT to unbind from the transcription factor complexes represented by RXR, RAR, T3R and PLZF.
