| First Author | Wagner SA | Year | 2016 |
| Journal | EMBO J | Volume | 35 |
| Issue | 17 | Pages | 1868-84 |
| PubMed ID | 27307491 | Mgi Jnum | J:235069 |
| Mgi Id | MGI:5792749 | Doi | 10.15252/embj.201694300 |
| Citation | Wagner SA, et al. (2016) SPATA2 links CYLD to the TNF-alpha receptor signaling complex and modulates the receptor signaling outcomes. EMBO J 35(17):1868-84 |
| abstractText | TNF-alpha is a key regulator of innate immune and proinflammatory responses. However, the composition of the TNF-alpha receptor-associated signaling complexes (TNF-RSC) and the architecture of the downstream signaling networks are incompletely understood. We employed quantitative mass spectrometry to demonstrate that TNF-alpha stimulation induces widespread protein phosphorylation and that the scope of phosphorylation expands in a temporal manner. TNF-alpha stimulation also induces rapid ubiquitylation of components of the TNF-RSC Temporal analysis of the TNF-RSC composition identified SPATA2 as a novel component of the TNF-RSC The predicted PUB domain in the N-terminus of SPATA2 interacts with the USP domain of CYLD, whereas the C-terminus of SPATA2 interacts with HOIP SPATA2 is required for recruitment of CYLD to the TNF-RSC Downregulation of SPATA2 augments transcriptional activation of NF-kappaB and inhibits TNF-alpha-induced necroptosis, pointing to an important function of SPATA2 in modulating the outcomes of TNF-alpha signaling. Taken together, our study draws a detailed map of TNF-alpha signaling, identifies SPATA2 as a novel component of TNF-alpha signaling, and provides a rich resource for further functional investigations. |
