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SHARPIN is a key regulator of immune and inflammatory responses
- Source :
- Journal of Cellular and Molecular Medicine
- Publication Year :
- 2012
-
Abstract
- Mice with spontaneous mutations in the Sharpin gene develop chronic proliferative dermatitis that is characterized by eosinophilic inflammation of the skin and other organs with increased expression of type 2 cytokines and dysregulated development of lymphoid tissues. The mutant mice share phenotypic features with human hypereosinophilic syndromes. The biological function of SHARPIN and how its absence leads to such a complex inflammatory phenotype in mice are poorly understood. However, recent studies identified SHARPIN as a novel modulator of immune and inflammatory responses. The emerging mechanistic model suggests that SHARPIN functions as an important adaptor component of the linear ubiquitin chain assembly complex that modulates activation of NF-κB signalling pathway, thereby regulating cell survival and apoptosis, cytokine production and development of lymphoid tissues. In this review, we will summarize the current understanding of the ubiquitin-dependent regulatory mechanisms involved in NF-κB signalling, and incorporate the recently obtained molecular insights of SHARPIN into this pathway. Recent studies identified SHARPIN as an inhibitor of β1-integrin activation and signalling, and this may be another mechanism by which SHARPIN regulates inflammation. Furthermore, the disrupted lymphoid organogenesis in SHARPIN-deficient mice suggests that SHARPIN-mediated NF-κB regulation is important for de novo development of lymphoid tissues.
- Subjects :
- Lymphoid Tissue
medicine.medical_treatment
Organogenesis
eosinophilic dermatitis
Gene Expression
Reviews
Inflammation
Apoptosis
Dermatitis
Nerve Tissue Proteins
scaly skin disease
ubiquitination
NF-κB
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Ubiquitin
lymphoid organogenesis
medicine
Animals
Humans
SHARPIN Gene
030304 developmental biology
0303 health sciences
biology
Integrin beta1
NF-kappa B
Cell Biology
NFKB1
chronic dermatitis
Hedgehog signaling pathway
Cell biology
immune system
Cytokine
Phenotype
chemistry
030220 oncology & carcinogenesis
Models, Animal
Mutation
biology.protein
Molecular Medicine
Cytokines
medicine.symptom
Signal transduction
Sharpin
Signal Transduction
Subjects
Details
- ISSN :
- 15824934
- Volume :
- 16
- Issue :
- 10
- Database :
- OpenAIRE
- Journal :
- Journal of cellular and molecular medicine
- Accession number :
- edsair.doi.dedup.....219f7bb79d879892d225eee321cbd676