Figure 3.

Post-translational regulation of NCoR1/SMRT. (A) Ubiquitination of NCoR1/SMRT (red sphere with halo; Ub) by TBLR, following phosphorylation of TBLR by upstream pathways, leads to their nuclear export and proteasomal degradation. (B) Growth factor and cytokine receptors (EGFR, IL-βR, etc.; see details in the text) signal through downstream kinases, such as MAP3K, AKT, and Cdk2, which phosphorylate NCoR1/SMRT (green sphere with halo; P). This triggers their export from the nucleus, enabling the docking of coactivators, as such derepressing transcription. (C) Conversely, sumoylation of NCoR1 (blue oval; SUMO) stabilizes the complex and enhances repressive activity. The color code for the members of the core repression complex (HDAC3, TBL1, TBLR1, and GPS2) is conserved throughout the figures.