Phosphorylation of retinoid X receptor suppresses its ubiquitination in human hepatocellular carcinoma

• DOI: 10.1053/jhep.2002.31164
• Publication Date: 2002-08-25T03:46:10Z
• Authors: Seiji Adachi; Masataka Okuno; Rie Matsushima-Ni...; Yukihiko Takano; Soichi Kojima; Scott L. Friedman; Hisataka Moriwaki; Yukio Okano
• Keywords: Retinoid X receptor

Retinoid X receptor alpha (RXRalpha) has emerged as an important nuclear involved in hepatocarcinogenesis, because its ligand suppresses the development of hepatocellular carcinoma (HCC) both experimental and clinical studies. We have demonstrated that phosphorylation RXRalpha at serine 260 interferes with function delays degradation cultured human HCC, leading to enhanced cellular proliferation. Here, we show normal liver nonproliferating hepatocyte cultures, is unphosphorylated highly ubiquitinated, rendering it sensitive proteasome-mediated degradation. On other hand, phosphoserine resistant ubiquitination HCC tissues a cell line, HuH7. In these cells, phosphorylated by mitogen-activated protein (MAP) kinase. proliferating hepatocytes, similar also ubiquitin-mediated proteasome, but this differentially regulated between cells hepatocytes. 9-cis retinoic acid (9cRA), RXRalpha, MAP kinase-mediated thereby enhances whereas fails exert effects cells. conclusion, switching ubiquitin/proteasome-dependent may be responsible for aberrant growth suppression retinoids.