Deubiquitinase CYLD acts as a negative regulator for bacterium NTHi-induced inflammation by suppressing K63-linked ubiquitination of MyD88
- 주제(키워드) CYLD , MyD88 , deubiquitinase , polyubiquitination
- 등재 SCIE, SCOPUS
- 발행기관 NATL ACAD SCIENCES
- 발행년도 2016
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000130449
- 본문언어 영어
- Published As http://dx.doi.org/10.1073/pnas.1518615113
초록/요약
Myeloid differentiation factor 88 (MyD88) acts as a crucial adaptor molecule for Toll-like receptors (TLRs) and interleukin (IL)-1 receptor signaling. In contrast to the well-studied positive regulation of MyD88 signaling, how MyD88 signaling is negatively regulated still remains largely unknown. Here, we demonstrate for the first time to our knowledge that MyD88 protein undergoes lysine 63 (K63)-linked polyubiquitination, which is functionally critical for mediating TLR-MyD88-dependent signaling. Deubiquitinase CYLD negatively regulates MyD88-mediated signaling by directly interacting with MyD88 and deubiquitinating nontypeable Haemophilus influenzae (NTHi)-induced K63-linked polyubiquitination of MyD88 at lysine 231. Importantly, we further confirmed this finding in the lungs of mice in vivo by using MyD88(-/-)CYLD(-/-) mice. Understanding how CYLD deubiquitinates K63-linked polyubiquitination of MyD88 may not only bring insights into the negative regulation of TLR-MyD88-dependent signaling, but may also lead to the development of a previously unidentified therapeutic strategy for uncontrolled inflammation.
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