論文 - 詳細
| RRC ID | 65977 |
|---|---|
| 著者 | Seo SK, Hwang CS, Choe TB, Hong SI, Yi JY, Hwang SG, Lee HG, Oh ST, Lee YH, Park IC. |
| タイトル | Selective inhibition of histone deacetylase 2 induces p53-dependent survivin downregulation through MDM2 proteasomal degradation. |
| ジャーナル | Oncotarget |
| Abstract |
In the present study, we found that selective inhibition of histone deacetylase 2 (HDAC2) with small inhibitory RNA (siRNA) induced survivin downregulation in a p53-dependent manner. Interestingly, suberoylanilide hydroxamic acid (SAHA) or knockdown of HDAC2 induced downregulation of Mdm2, a negative regulator of p53, at the protein level. SAHA and/or HDAC2 siRNA increased Mdm2 ubiquitination, and MG132, an inhibitor of proteosome function, prevented HDAC2 inhibition-induced degradation of Mdm2. Clinically, the mRNA levels of HDAC2 and survivin were prominently overexpressed in lung cancer patients compared to normal lung tissues. Silencing of HDAC2 enhanced the cell death caused by ionizing radiation in lung cancer cells. Collectively, our results indicate that selective inhibition of HDAC2 causes survivin downregulation through activation of p53, which is mediated by downregulation of Mdm2. They further suggest that HDAC2 may exert a dominant effect on lung cancer cell survival by sustaining Mdm2-survivin levels. |
| 巻・号 | 6(28) |
| ページ | 26528-40 |
| 公開日 | 2015-9-22 |
| DOI | 10.18632/oncotarget.3100 |
| PII | 3100 |
| PMID | 25605253 |
| PMC | PMC4694920 |
| MeSH | Cell Death / drug effects Cell Death / radiation effects Cell Line, Tumor Down-Regulation Histone Deacetylase 2 / antagonists & inhibitors* Histone Deacetylase 2 / genetics Histone Deacetylase 2 / metabolism Histone Deacetylase Inhibitors / pharmacology* Humans Inhibitor of Apoptosis Proteins / genetics Inhibitor of Apoptosis Proteins / metabolism* Lung Neoplasms / drug therapy* Lung Neoplasms / enzymology Lung Neoplasms / genetics Lung Neoplasms / pathology Proteasome Endopeptidase Complex / genetics Proteasome Endopeptidase Complex / metabolism* Proteasome Inhibitors / pharmacology Proteolysis Proto-Oncogene Proteins c-mdm2 / genetics Proto-Oncogene Proteins c-mdm2 / metabolism* RNA Interference Survivin Transfection Tumor Suppressor Protein p53 / genetics Tumor Suppressor Protein p53 / metabolism* Ubiquitination |
| IF | 5.168 |
| リソース情報 | |
| ヒト・動物細胞 | Lu99(RCB1900) |