Nucleophosmin (NPM1/B23) Interacts with Activating Transcription Factor 5 (ATF5) Protein and Promotes Proteasome- and Caspase-dependent ATF5 Degradation in Hepatocellular Carcinoma Cells
文献类型：期刊论文
| 作者 | Liu, XJ; Liu, D; Qian, DM; Dai, J; An, Y; Jiang, SY; Stanley, B; Yang, JM; Wang, B; Liu, XY |
| 刊名 | JOURNAL OF BIOLOGICAL CHEMISTRY
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| 出版日期 | 2012 |
| 卷号 | 287期号:23页码:19599-19609 |
| 通讯作者 | Liu, DX (reprint author), Penn State Coll Med, Hershey, PA 17033 USA.,dliu@psu.edu |
| 英文摘要 | Nucleophosmin (NPM1/B23) and the activating transcription factor 5 (ATF5) are both known to subject to cell type-dependent regulation. NPM1 is expressed weakly in hepatocytes and highly expressed in hepatocellular carcinomas (HCC) with a clear correlation between enhanced NPM1 expression and increased tumor grading and poor prognosis, whereas in contrast, ATF5 is expressed abundantly in hepatocytes and down-regulated in HCC. Re-expression of ATF5 in HCC inhibits cell proliferation. We report here that using an unbiased approach, tandem affinity purification (TAP) followed with mass spectrometry (MS), we identified NPM1 as a novel ATF5-interacting protein. Unlike many other NPM1-interacting proteins that interact with the N-terminal oligomerization domain of NPM1, ATF5 binds via its basic leucine zipper to the C-terminal region of NPM1 where its nucleolar localization signal is located. NPM1 association with ATF5, whose staining patterns partially overlap in the nucleoli, promotes ATF5 protein degradation through proteasome-dependent and caspase-dependent pathways. NPM1-c, a mutant NPM1 that is defective in nucleolar localization, failed to stimulate ATF5 polyubiquitination and was unable to down-regulate ATF5. NPM1 interaction with ATF5 displaces HSP70, a known ATF5-interacting protein, from ATF5 protein complexes and antagonizes its role in stabilization of ATF5 protein. NPM1-promoted ATF5 down-regulation diminished ATF5-mediated repression of cAMP-responsive element-dependent gene transcription and abrogates ATF5-induced G(2)/M cell cycle blockade and inhibition of cell proliferation in HCC cells. Our study establishes a mechanistic link between elevated NPM1 expression and depressed ATF5 in HCC and suggests that regulation of ATF5 by NPM1 plays an important role in the proliferation and survival of HCC. |
| 学科主题 | Biochemistry & Molecular Biology |
| 类目[WOS] | Biochemistry & Molecular Biology |
| 关键词[WOS] | ARF TUMOR-SUPPRESSOR ; NEURAL PROGENITOR CELLS ; BREAST-CANCER CELLS ; CENTROSOME DUPLICATION ; HISTONE CHAPERONE ; GENE-EXPRESSION ; G(2)-M ARREST ; C6 GLIOMA ; TARGET ; PROLIFERATION |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000306411900071 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.143/handle/331003/687]  |
| 专题 | 上海生化细胞研究所_上海生科院生化细胞研究所 |
| 推荐引用方式 GB/T 7714 | Liu, XJ,Liu, D,Qian, DM,et al. Nucleophosmin (NPM1/B23) Interacts with Activating Transcription Factor 5 (ATF5) Protein and Promotes Proteasome- and Caspase-dependent ATF5 Degradation in Hepatocellular Carcinoma Cells[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2012,287(23):19599-19609. |
| APA | Liu, XJ.,Liu, D.,Qian, DM.,Dai, J.,An, Y.,...&Liu, DX.(2012).Nucleophosmin (NPM1/B23) Interacts with Activating Transcription Factor 5 (ATF5) Protein and Promotes Proteasome- and Caspase-dependent ATF5 Degradation in Hepatocellular Carcinoma Cells.JOURNAL OF BIOLOGICAL CHEMISTRY,287(23),19599-19609. |
| MLA | Liu, XJ,et al."Nucleophosmin (NPM1/B23) Interacts with Activating Transcription Factor 5 (ATF5) Protein and Promotes Proteasome- and Caspase-dependent ATF5 Degradation in Hepatocellular Carcinoma Cells".JOURNAL OF BIOLOGICAL CHEMISTRY 287.23(2012):19599-19609. |
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