期刊
HEPATOLOGY
卷 55, 期 4, 页码 1237-1248出版社
WILEY
DOI: 10.1002/hep.24795
关键词
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资金
- NIH [DK51719, AT-1576, AT004896, SAF2005-00855, ETORTEK-2011]
- Programa Ramon y Cajal [FIS PS09/00094, FIS PS09/02010, FIS Pl10/01484, FIS Pl11/01588]
- Sanidad Gobiemo Vasco
- Education Gobierno Vasco
Hu antigen R (HuR) is a central RNA-binding protein regulating cell dedifferentiation, proliferation, and survival, which are well-established hallmarks of cancer. HuR is frequently overexpressed in tumors correlating with tumor malignancy, which is in line with a role for HuR in tumorigenesis. However, the precise mechanism leading to changes in HuR expression remains unclear. In the liver, HuR plays a crucial role in hepatocyte proliferation, differentiation, and transformation. Here, we unraveled a novel mean of regulation of HuR expression in hepatocellular carcinoma (HCC) and colon cancer. HuR levels correlate with the abundance of the oncogene, murine double minute 2 (Mdm2), in human HCC and colon cancer metastases. HuR is stabilized by Mdm2-mediated NEDDylation in at least three lysine residues, ensuring its nuclear localization and protection from degradation. Conclusion: This novel Mdm2/NEDD8/HuR regulatory framework is essential for the malignant transformation of tumor cells, which, in turn, unveils a novel signaling paradigm that is pharmacologically amenable for cancer therapy. (Hepatology 2012)
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