Figure 2.

A schematic representation of RXRα phosphorylation in HCC cells. In normal hepatocytes, when the ligand (retinoid) binds to and activates RXRα, the receptor becomes able to heterodimerize with other nuclear receptors, including RAR, and then activates the expression of the target genes, which may regulate normal cell proliferation and differentiation, by binding to the specific responsive element. In HCC cells, the Ras/MAPK pathway is highly activated and phosphorylates RXRα at serine residues, thus impairing the functions of the receptor. Therefore, the accumulated p-RXRα interferes with the remaining normal RXRα, presumably, in a dominant negative manner, thereby playing a critical role in the development of HCC. L: ligand. Ub: ubiquitin.