Inactivation of BAD by IKK Inhibits TNF alpha-Induced Apoptosis Independently of NF-kappa B Activation

	Inactivation of BAD by IKK Inhibits TNF alpha-Induced Apoptosis Independently of NF-kappa B Activation
	Yan, J; Xiang, JL; Lin, YT; Ma, JG; Zhang, JY; Zhang, H; Sun, JS; Danial, NN; Liu, J; Lin, AN
刊名	CELL
	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
内容类型	期刊论文
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.