Tumor Protein p63/Nuclear Factor kappa B Feedback Loop in Regulation of Cell Death
文献类型：期刊论文
| 作者 | Luo, Zhen-Ge
|
| 刊名 | JOURNAL OF BIOLOGICAL CHEMISTRY
 |
| 出版日期 | 2011 |
| 卷号 | 286期号:50页码:43204-43213 |
| 关键词 | DNA-DAMAGE P53 FAMILY TRANSCRIPTIONAL REGULATION INDUCED APOPTOSIS CARCINOMA-CELLS CROSS-TALK IN-VIVO CANCER AUTOPHAGY DELTA-NP63-ALPHA |
| ISSN号 | 0021-9258 |
| 通讯作者 | Ratovitski, EA (reprint author), Johns Hopkins Univ, Sch Med, Dept Otolaryngol Head & Neck Surg, Div Head & Neck Canc Res, Canc Res Bldg 2,Rm 2M05,1550 Orleans St, Baltimore, MD 21231 USA,eratovi1@jhmi.edu |
| 英文摘要 | Tumor protein (TP)-p53 family members often play proapoptotic roles, whereas nuclear factor kappa B (NF-kappa B) functions as a proapoptotic and antiapoptotic regulator depending on the cellular environment. We previously showed that the NF-kappa B activation leads to the reduction of the TP63 isoform, Delta Np63 alpha, thereby rendering the cells susceptible to cell death upon DNA damage. However, the functional relationship between TP63 isotypes and NF-kappa B is poorly understood. Here, we report that the TAp63 regulates NF-kappa B transcription and protein stability subsequently leading to the cell death phenotype. We found that TAp63 beta induced the expression of the p65 subunit of NF-kappa B (RELA) and target genes involved in cell cycle arrest or apoptosis, thereby triggering cell death pathways in MCF10A cells. RELA was shown to concomitantly modulate specific cell survival pathways, making it indispensable for the TAp63 beta-dependent regulation of cell death. We showed that TAp63 beta and RELA formed protein complexes resulted in their mutual stabilization and inhibition of the RELA ubiquitination. Finally, we showed that TAp63 beta directly induced RelA transcription by binding to and activating of its promoter and, in turn, leading to activation of the NF-kappa B-dependent cell death genes. Overall, our data defined the regulatory feedback loop between TAp63 beta and NF-kappa B involved in the activation of cell death process of cancer cells. |
| 学科主题 | Biochemistry & Molecular Biology |
| 收录类别 | SCI |
| 资助信息 | National Institute of Health through the NIDCR[R01-DE13561]; National Institute of Health through the NEI[R01-EY018636-01] |
| 语种 | 英语 |
| 公开日期 | 2012-07-13 |
| 源URL | [http://ir.sibs.ac.cn/handle/331001/1515]  |
| 专题 | 上海神经科学研究所_神经所(总) 上海神经科学研究所_突触信号研究组 |
| 推荐引用方式 GB/T 7714 | Luo, Zhen-Ge. Tumor Protein p63/Nuclear Factor kappa B Feedback Loop in Regulation of Cell Death[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2011,286(50):43204-43213. |
| APA | Luo, Zhen-Ge.(2011).Tumor Protein p63/Nuclear Factor kappa B Feedback Loop in Regulation of Cell Death.JOURNAL OF BIOLOGICAL CHEMISTRY,286(50),43204-43213. |
| MLA | Luo, Zhen-Ge."Tumor Protein p63/Nuclear Factor kappa B Feedback Loop in Regulation of Cell Death".JOURNAL OF BIOLOGICAL CHEMISTRY 286.50(2011):43204-43213. |
入库方式： OAI收割
来源：上海神经科学研究所
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