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USP15 Deubiquitinates CARD9 to Downregulate C-Type Lectin Receptor–Mediated Signaling
- Source :
- Immunohorizons
- Publication Year :
- 2020
- Publisher :
- The American Association of Immunologists, 2020.
-
Abstract
- Posttranslational modifications are efficient means to rapidly regulate protein function in response to a stimulus. Although ubiquitination events and the E3 ubiquitin ligases involved are increasingly characterized in many signaling pathways, their regulation by deubiquitinating enzymes remains less understood. The C-type lectin receptor (CLR) signaling adaptor CARD9 was previously reported to be activated via TRIM62-mediated ubiquitination. In this study, we identify the deubiquitinase USP15 as a novel regulator of CARD9, demonstrating that USP15 constitutively associates with CARD9 and removes TRIM62-deposited ubiquitin marks. Furthermore, USP15 knockdown and knockout specifically enhance CARD9-dependent CLR signaling in both mouse and human immune cells. Altogether, our study identifies a novel regulator of innate immune signaling and provides a blueprint for the identification of additional deubiquitinases that are likely to control these processes.
- Subjects :
- Ubiquitin-Protein Ligases
Immunology
Regulator
Article
Deubiquitinating enzyme
Tripartite Motif Proteins
Mice
Ubiquitin
Downregulation and upregulation
C-type lectin
Animals
Humans
Immunology and Allergy
Lectins, C-Type
Receptor
Innate immune system
biology
Ubiquitination
General Medicine
Cell biology
CARD Signaling Adaptor Proteins
HEK293 Cells
biology.protein
Ubiquitin-Specific Proteases
Signal transduction
Protein Processing, Post-Translational
Protein Binding
Signal Transduction
Subjects
Details
- ISSN :
- 25737732
- Volume :
- 4
- Database :
- OpenAIRE
- Journal :
- ImmunoHorizons
- Accession number :
- edsair.doi.dedup.....25aa5024624e8db683aea34c8ea84a42