TY - JOUR
T1 - Murine double minute 2 regulates Hu antigen R stability in human liver and colon cancer through NEDDylation
AU - Embade, Nieves
AU - Fernández-Ramos, David
AU - Varela-Rey, Marta
AU - Beraza, Naiara
AU - Sini, Marcella
AU - de Juan, Virginia Gutiérrez
AU - Woodhoo, Ashwin
AU - Martínez-López, Nuria
AU - Rodríguez-Iruretagoyena, Begoña
AU - Bustamante, Francisco Javier
AU - de la Hoz, Ana Belén
AU - Carracedo, Arkaitz
AU - Xirodimas, Dimitris P.
AU - Rodríguez, Manuel S.
AU - Lu, Shelly C.
AU - Mato, José M.
AU - Martínez-Chantar, María L.
PY - 2012/4
Y1 - 2012/4
N2 - 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.
AB - 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.
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U2 - 10.1002/hep.24795
DO - 10.1002/hep.24795
M3 - Article
C2 - 22095636
AN - SCOPUS:84859158017
SN - 0270-9139
VL - 55
SP - 1237
EP - 1248
JO - Hepatology
JF - Hepatology
IS - 4
ER -
