Reference - Detail
| RRC ID | 37698 |
|---|---|
| Author | Nishimura T, Kohara M, Izumi K, Kasama Y, Hirata Y, Huang Y, Shuda M, Mukaidani C, Takano T, Tokunaga Y, Nuriya H, Satoh M, Saito M, Kai C, Tsukiyama-Kohara K. |
| Title | Hepatitis C virus impairs p53 via persistent overexpression of 3beta-hydroxysterol Delta24-reductase. |
| Journal | J Biol Chem |
| Abstract |
Persistent infection with hepatitis C virus (HCV) induces tumorigenicity in hepatocytes. To gain insight into the mechanisms underlying this process, we generated monoclonal antibodies on a genome-wide scale against an HCV-expressing human hepatoblastoma-derived cell line, RzM6-LC, showing augmented tumorigenicity. We identified 3beta-hydroxysterol Delta24-reductase (DHCR24) from this screen and showed that its expression reflected tumorigenicity. HCV induced the DHCR24 overexpression in human hepatocytes. Ectopic or HCV-induced DHCR24 overexpression resulted in resistance to oxidative stress-induced apoptosis and suppressed p53 activity. DHCR24 overexpression in these cells paralleled the increased interaction between p53 and MDM2 (also known as HDM2), a p53-specific E3 ubiquitin ligase, in the cytoplasm. Persistent DHCR24 overexpression did not alter the phosphorylation status of p53 but resulted in decreased acetylation of p53 at lysine residues 373 and 382 in the nucleus after treatment with hydrogen peroxide. Taken together, these results suggest that DHCR24 is elevated in response to HCV infection and inhibits the p53 stress response by stimulating the accumulation of the MDM2-p53 complex in the cytoplasm and by inhibiting the acetylation of p53 in the nucleus. |
| Volume | 284(52) |
| Pages | 36442-36452 |
| Published | 2009-12-25 |
| DOI | 10.1074/jbc.M109.043232 |
| PII | S0021-9258(20)37455-X |
| PMID | 19861417 |
| PMC | PMC2794760 |
| MeSH | Acetylation / drug effects Animals Apoptosis / drug effects Apoptosis / genetics Cell Nucleus / genetics Cell Nucleus / metabolism Cell Transformation, Viral* Cytoplasm / genetics Cytoplasm / metabolism Enzyme Induction / genetics Genome-Wide Association Study Hep G2 Cells Hepacivirus* Hepatitis C / genetics Hepatitis C / metabolism* Hepatocytes / metabolism* Humans Hydrogen Peroxide / pharmacology Mice Mice, Inbred BALB C Mice, Nude Nerve Tissue Proteins / biosynthesis* Nerve Tissue Proteins / genetics Oxidants / pharmacology Oxidative Stress / drug effects Oxidative Stress / genetics Oxidoreductases Acting on CH-CH Group Donors / biosynthesis* Oxidoreductases Acting on CH-CH Group Donors / genetics Phosphorylation / drug effects Phosphorylation / genetics Proto-Oncogene Proteins c-mdm2 / genetics Proto-Oncogene Proteins c-mdm2 / metabolism Tumor Suppressor Protein p53 / genetics Tumor Suppressor Protein p53 / metabolism* |
| IF | 4.238 |
| Times Cited | 41 |
| WOS Category | BIOCHEMISTRY & MOLECULAR BIOLOGY |
| Altmetric score |
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| The most frequently cited source | Youtube |
| Total number of mentions | 1 |
| Altmetric score changes over past 6months | 0.2 |
| Resource | |
| Human and Animal Cells | |