| First Author | Lin M | Year | 2016 |
| Journal | Mol Cell | Volume | 64 |
| Issue | 2 | Pages | 267-281 |
| PubMed ID | 27692986 | Mgi Jnum | J:248785 |
| Mgi Id | MGI:6094410 | Doi | 10.1016/j.molcel.2016.08.029 |
| Citation | Lin M, et al. (2016) USP38 Inhibits Type I Interferon Signaling by Editing TBK1 Ubiquitination through NLRP4 Signalosome. Mol Cell 64(2):267-281 |
| abstractText | TBK1 is a component of the type I interferon (IFN) signaling pathway, yet the mechanisms controlling its activity and degradation remain poorly understood. Here we report that USP38 negatively regulates type I IFN signaling by targeting the active form of TBK1 for degradation in vitro and in vivo. USP38 specifically cleaves K33-linked poly-ubiquitin chains from TBK1 at Lys670, and it allows for subsequent K48-linked ubiquitination at the same position mediated by DTX4 and TRIP. Knockdown or knockout of USP38 increases K33-linked ubiquitination, but it abrogates K48-linked ubiquitination and degradation of TBK1, thus enhancing type I IFN signaling. Our findings identify an essential role for USP38 in negatively regulating type I IFN signaling, and they provide insights into the mechanisms by which USP38 regulates TBK1 ubiquitination through the NLRP4 signalosome. |
