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Miz1 is a signal- and pathway-specific modulator or regulator (SMOR) that suppresses TNF-alpha-induced JNK1 activation | |
2009 | |
发表期刊 | PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA |
ISSN | 0027-8424 |
卷号 | 106期号:43页码:18279-18284 |
发表状态 | 已发表 |
DOI | 10.1073/pnas.0906328106 |
摘要 | The proinflammatory cytokine TNF-alpha exerts its pleiotropic functions through activation of multiple downstream effectors, including JNK1. Yet, the underlying regulatory mechanism is incompletely understood. Here, we report that the transcription factor Myc-interacting zinc-finger protein 1 (Miz1) selectively suppresses TNF-alpha-induced JNK1 activation and cell death independently of its transcription activity. Proteomics analysis and yeast two-hybrid screening reveal that Miz1 is a JNK-associated protein. The TNF-alpha induced activation of JNK1 is augmented in Miz1-deficient mouse embryonic fibroblasts (Miz1(-/-) MEFs), but the augmentation is abrogated by reintroduction of Miz1 or its transcription-deficient mutant. The regulation by Miz1 is highly specific, because it regulates TNF-alpha-induced TRAF2 K63-linked polyubiquitination. Neither JNK1 activation by IL-1 beta or UV nor TNF-alpha-induced activation of p38, ERK, or I kappa B kinase complex is affected by the loss of Miz1. The TNF-alpha-induced cell death also is accelerated in Miz1(-/-) MEFs. Upon TNF-alpha stimulation, Miz1 is degraded rapidly by the proteasome, relieving its suppression on JNK1 activation. Thus, our results show that in addition to being a transcription factor Miz1 acts as a signal-and pathway-specific modulator or regulator that specifically regulates TNF-alpha-induced JNK1 activation and cell death. |
URL | 查看原文 |
WOS研究方向 | Science & Technology - Other Topics |
WOS类目 | Multidisciplinary Sciences |
WOS记录号 | WOS:000271222500044 |
WOS关键词 | NF-KAPPA-B ; INDUCED CELL-DEATH ; PROTEIN-KINASE ; IKK-BETA ; JUN KINASES ; IDENTIFICATION ; APOPTOSIS ; PHOSPHORYLATION ; INHIBITION ; INDUCTION |
原始文献类型 | Article |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/120779 |
专题 | 个人在本单位外知识产出 |
通讯作者 | Liu, Jing; Lin, Anning |
作者单位 | 1.Univ Chicago, Ben May Dept Canc Res, Chicago, IL 60637 USA 2.Univ Marburg, Inst Mol Biol & Tumour Res, D-35033 Marburg, Germany |
推荐引用方式 GB/T 7714 | Liu, Jing,Zhao, Yingming,Eilers, Martin,et al. Miz1 is a signal- and pathway-specific modulator or regulator (SMOR) that suppresses TNF-alpha-induced JNK1 activation[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,2009,106(43):18279-18284. |
APA | Liu, Jing,Zhao, Yingming,Eilers, Martin,&Lin, Anning.(2009).Miz1 is a signal- and pathway-specific modulator or regulator (SMOR) that suppresses TNF-alpha-induced JNK1 activation.PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,106(43),18279-18284. |
MLA | Liu, Jing,et al."Miz1 is a signal- and pathway-specific modulator or regulator (SMOR) that suppresses TNF-alpha-induced JNK1 activation".PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 106.43(2009):18279-18284. |
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