1. Deubiquitinase CYLD acts as a negative regulator for bacterium NTHi-induced inflammation by suppressing K63-linked ubiquitination of MyD88
- Author
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Masanori Miyata, Jae Hyang Lim, Jian Dong Li, and Byung Cheol Lee
- Subjects
0301 basic medicine ,Lysine ,Inflammation ,Plasma protein binding ,Models, Biological ,Deubiquitinating enzyme ,03 medical and health sciences ,Mice ,Ubiquitin ,medicine ,Animals ,Humans ,Receptor ,Polyubiquitin ,Multidisciplinary ,biology ,Tumor Suppressor Proteins ,Ubiquitination ,Interleukin ,hemic and immune systems ,Haemophilus influenzae ,Deubiquitinating Enzyme CYLD ,Cysteine Endopeptidases ,030104 developmental biology ,PNAS Plus ,Myeloid Differentiation Factor 88 ,biology.protein ,Cancer research ,medicine.symptom ,HeLa Cells ,Protein Binding - Abstract
Significance Despite the critical role for myeloid differentiation factor 88 (MyD88) in mediating pathogen-induced innate and adaptive immune responses, how functional activity of MyD88 is tightly controlled remains unknown. Among various types of posttranslational modification, ubiquitination and deubiquitination of host signaling molecules play an important role in tightly regulating immune response. However, inducible ubiquitination, in particular proteolysis-independent polyubiquitination as well as deubiquitination of MyD88, remains largely unclear. Here, we demonstrate that deubiquitinase CYLD negatively regulates MyD88-mediated inflammation by directly interacting with MyD88 and deubiquitinating nontypeable Haemophilus influenzae -induced lysine 63-linked polyubiquitination of MyD88. Thus, our studies may not only bring insights into the negative regulation of Toll-like receptor–MyD88-dependent signaling but may also lead to the development of a previously unidentified therapeutic strategy for uncontrolled inflammation.
- Published
- 2016