Inactivation of BAD by IKK Inhibits TNF alpha-Induced Apoptosis Independently of NF-kappa B Activation
文献类型：期刊论文
| 作者 | Yan, J; Xiang, JL; Lin, YT; Ma, JG; Zhang, JY; Zhang, H; Sun, JS; Danial, NN; Liu, J; Lin, AN |
| 刊名 | CELL
 |
| 出版日期 | 2013 |
| 卷号 | 152期号:1页码:304-315 |
| 通讯作者 | Lin, AN (reprint author), Univ Chicago, Ben May Dept Canc Res, Chicago, IL 60637 USA.,anninglin@bsd.uchicago.edu |
| 英文摘要 | The I kappa B kinase complex (IKK) is a key regulator of immune responses, inflammation, cell survival, and tumorigenesis. The prosurvival function of IKK centers on activation of the transcription factor NF-kappa B, whose target gene products inhibit caspases and prevent prolonged JNK activation. Here, we report that inactivation of the BH3-only protein BAD by IKK independently of NF-kappa B activation suppresses TNF alpha-induced apoptosis. TNF alpha-treated Ikk beta(-/-) mouse embryonic fibroblasts (MEFs) undergo apoptosis significantly faster than MEFs deficient in both RelA and cRel due to lack of inhibition of BAD by IKK. IKK phosphorylates BAD at serine-26 (Ser26) and primes it for inactivation. Elimination of Ser26 phosphorylation promotes BAD proapoptotic activity, thereby accelerating TNF alpha-induced apoptosis in cultured cells and increasing mortality in animals. Our results reveal that IKK inhibits TNF alpha-induced apoptosis through two distinct but cooperative mechanisms: activation of the survival facto r NF-kappa B and inactivation of the proapoptotic BH3-only BAD protein. |
| 学科主题 | Biochemistry & Molecular Biology; Cell Biology |
| 类目[WOS] | Biochemistry & Molecular Biology ; Cell Biology |
| 关键词[WOS] | TUMOR-NECROSIS-FACTOR ; SEVERE LIVER DEGENERATION ; CELL-DEATH ; TRANSCRIPTION FACTORS ; SIGNAL-TRANSDUCTION ; FEEDBACK INHIBITION ; KINASE ACTIVATION ; JNK ACTIVATION ; DEFICIENT MICE ; PHOSPHORYLATION |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000313719800025 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.143/handle/331003/484]  |
| 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 | Yan, J,Xiang, JL,Lin, YT,et al. Inactivation of BAD by IKK Inhibits TNF alpha-Induced Apoptosis Independently of NF-kappa B Activation[J]. CELL,2013,152(1):304-315. |
| APA | Yan, J.,Xiang, JL.,Lin, YT.,Ma, JG.,Zhang, JY.,...&Lin, AN.(2013).Inactivation of BAD by IKK Inhibits TNF alpha-Induced Apoptosis Independently of NF-kappa B Activation.CELL,152(1),304-315. |
| MLA | Yan, J,et al."Inactivation of BAD by IKK Inhibits TNF alpha-Induced Apoptosis Independently of NF-kappa B Activation".CELL 152.1(2013):304-315. |
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