The Ski protein can inhibit ligand induced RARalpha and HDAC3 degradation in the retinoic acid signaling pathway.

Recent data has implicated the Ski protein as being a physiologically relevant negative regulator of signaling by retinoic acid (RA). The mechanism by which Ski represses RA signaling is unknown. Co-immunoprecipitation and immunofluorescence assay showed that Ski and RARalpha are in the same complex in both the absence and presence of RA, which makes Ski different from other corepressors. We determined that Ski can stabilize RARalpha and HDAC3. These results suggest that Ski represses RA signaling by stabilizing corepressor complex.