期刊
EMBO REPORTS
卷 17, 期 10, 页码 1485-1497出版社
WILEY
DOI: 10.15252/embr.201642592
关键词
apoptosis; CYLD; HOIP; SPATA2; TNF
资金
- Centre for Biological Signalling Studies (BIOSS), Freiburg, Germany - Excellence Initiative of the German Federal and State Governments, Germany [EXC-294]
- Spemann Graduate School of Biology and Medicine (SGBM), Freiburg, Germany - Excellence Initiative of the German Federal and State Governments, Germany [GSC-4]
- Deutsche Krebshilfe [112140]
K63- and Met1-linked ubiquitylation are crucial posttranslational modifications for TNF receptor signaling. These non-degradative ubiquitylations are counteracted by deubiquitinases (DUBs), such as the enzyme CYLD, resulting in an appropriate signal strength, but the regulation of this process remains incompletely understood. Here, we describe an interaction partner of CYLD, SPATA2, which we identified by a mass spectrometry screen. We find that SPATA2 interacts via its PUB domain with CYLD, while a PUB interaction motif (PIM) of SPATA2 interacts with the PUB domain of the LUBAC component HOIP. SPATA2 is required for the recruitment of CYLD to the TNF receptor signaling complex upon TNFR stimulation. Moreover, SPATA2 acts as an allosteric activator for the K63- and M1-deubiquitinase activity of CYLD. In consequence, SPATA2 substantially attenuates TNF-induced NF-kappa B and MAPK signaling. Conversely, SPATA2 is required for TNF-induced complex II formation, caspase activation, and apoptosis. Thus, this study identifies SPATA2 as an important factor in the TNF signaling pathway with a substantial role for the effects mediated by the cytokine.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据