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Title: Tumor Protein p63/Nuclear Factor kappa B Feedback Loop in Regulation of Cell Death
Author: Sen, Tanusree ; Sen, Nilkantha ; Huang, Yiping ; Sinha, Debasish ; null(罗振革) ; Ratovitski, Edward A. ; Sidransky, David
Source: JOURNAL OF BIOLOGICAL CHEMISTRY
Issued Date: 2011
Volume: 286, Issue:50, Pages:43204-43213
Keyword: DNA-DAMAGE ; P53 FAMILY ; TRANSCRIPTIONAL REGULATION ; INDUCED APOPTOSIS ; CARCINOMA-CELLS ; CROSS-TALK ; IN-VIVO ; CANCER ; AUTOPHAGY ; DELTA-NP63-ALPHA
Subject: Biochemistry & Molecular Biology
Corresponding Author: 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
English Abstract: 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.
Indexed Type: sci
Language: 英语
Content Type: 期刊论文
URI: http://ir.sibs.ac.cn/handle/331001/1515
Appears in Collections:神经所(总)_期刊论文
突触信号研究组_期刊论文

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Recommended Citation:
Sen, Tanusree; Sen, Nilkantha; Huang, Yiping; Sinha, Debasish; Luo, Zhen-Ge; Ratovitski, Edward A.; Sidransky, David.Tumor Protein p63/Nuclear Factor kappa B Feedback Loop in Regulation of Cell Death,JOURNAL OF BIOLOGICAL CHEMISTRY,2011,286(50):43204-43213
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