Unknown

Dataset Information

0

Murine double minute 2 regulates Hu antigen R stability in human liver and colon cancer through NEDDylation.


ABSTRACT: 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.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.

SUBMITTER: Embade N 

PROVIDER: S-EPMC3298572 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature

altmetric image

Publications


<h4>Unlabelled</h4>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 transformat  ...[more]

Similar Datasets

| S-EPMC5609474 | biostudies-literature
| S-EPMC5732819 | biostudies-other
| S-EPMC3810835 | biostudies-other
| S-EPMC9209722 | biostudies-literature
| S-EPMC7279848 | biostudies-literature
| S-EPMC6916148 | biostudies-literature
| S-EPMC6780965 | biostudies-literature
| S-EPMC4333419 | biostudies-other
| S-EPMC4483582 | biostudies-literature
| S-EPMC6199579 | biostudies-literature