Site-specific ubiquitination is required for relieving the transcription factor Miz1-mediated suppression on TNF-alpha-induced JNK activation and inflammation

	Site-specific ubiquitination is required for relieving the transcription factor Miz1-mediated suppression on TNF-alpha-induced JNK activation and inflammation
	Liu, J; Yan, J; Jiang, S; Wen, J; Chen, L; Zhao, YM; Lin, AN
刊名	PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
	2012
卷号	109 期号:1 页码:191-196
关键词	TNF receptor complex protein kinase
通讯作者	Lin, AN (reprint author), Univ Chicago, Ben May Dept Canc Res, Chicago, IL 60637 USA.,alin@sibcb.ac.cn
英文摘要	The transcription factor zinc-finger protein Miz1 represses TNF-alpha-induced JNK activation and the repression is relieved upon TNF-alpha stimulation. However, the underlying mechanism is incompletely understood. Here we report that Miz1 interferes with the ubiquitin conjugating enzyme (E2) Ubc13 for binding to the RING domain of TNF-receptor associated factor 2 (TRAF2), thereby inhibiting the ubiquitin ligase (E3) activity of TRAF2 and suppressing TNF-alpha-induced JNK activation. Upon TNF-alpha stimulation, Miz1 rapidly undergoes K48-linked polyubiquitination at Lys388 and Lys472 residues and subsequent proteasomal degradation in a TRAF2-dependent manner. Replacement of Lysine 388 and Lysine 472 by arginines generates a nondegradable Miz1 mutant, which significantly suppresses TNF-alpha-induced JNK1 activation and inflammation. Thus, our results reveal a molecular mechanism by which the repression of TNF-alpha-induced JNK activation by Miz1 is de-repressed by its own site-specific ubiquitination and degradation, which may account for the temporal control of TNF-alpha-JNK signaling.
学科主题	Science & Technology - Other Topics
类目[WOS]	Multidisciplinary Sciences
关键词[WOS]	NF-KAPPA-B ; TUMOR-NECROSIS-FACTOR ; CONJUGATING ENZYME ; CELL-DEATH ; IKK-BETA ; CHEMICAL HEPATOCARCINOGENESIS ; KINASE ACTIVATION ; JUN KINASES ; APOPTOSIS ; TRAF2
收录类别	SCI
语种	英语
WOS记录号	WOS:000298876500041
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/531]
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, J,Yan, J,Jiang, S,et al. Site-specific ubiquitination is required for relieving the transcription factor Miz1-mediated suppression on TNF-alpha-induced JNK activation and inflammation[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,2012,109(1):191-196.
APA	Liu, J.,Yan, J.,Jiang, S.,Wen, J.,Chen, L.,...&Lin, AN.(2012).Site-specific ubiquitination is required for relieving the transcription factor Miz1-mediated suppression on TNF-alpha-induced JNK activation and inflammation.PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,109(1),191-196.
MLA	Liu, J,et al."Site-specific ubiquitination is required for relieving the transcription factor Miz1-mediated suppression on TNF-alpha-induced JNK activation and inflammation".PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 109.1(2012):191-196.