Genetic relationships between A20/TNFAIP3, chronic inflammation and autoimmune disease.

Abstract

A20 [also known as TNFAIP3 (tumour necrosis factor α-induced protein 3)] restricts and terminates inflammatory responses through modulation of the ubiquitination status of central components in NF-κB (nuclear factor κB), IRF3 (interferon regulatory factor 3) and apoptosis signalling cascades. The phenotype of mice with full or conditional A20 deletion illustrates that A20 expression is essential to prevent chronic inflammation and autoimmune pathology. In addition, polymorphisms within the A20 genomic locus have been associated with multiple inflammatory and autoimmune disorders, including SLE (systemic lupus erythaematosis), RA (rheumatoid arthritis), Crohn's disease and psoriasis. A20 has also been implicated as a tumour suppressor in several subsets of B-cell lymphomas. The present review outlines recent findings that illustrate the effect of A20 defects in disease pathogenesis and summarizes the identified A20 polymorphisms associated with different immunopathologies.

• Authors: Lars Vereecke, Rudi Beyaert, Geert van Loo
• Journal: Biochemical Society transactions (Biochem Soc Trans) Vol. 39 Issue 4 Pg. 1086-91 (Aug 2011) ISSN: 1470-8752 [Electronic] England
• PMID: 21787353 (Publication Type: Journal Article, Review)

Chemical References

• DNA-Binding Proteins
• Intracellular Signaling Peptides and Proteins
• Nuclear Proteins
• TNFAIP3 protein, human
• Tumor Necrosis Factor alpha-Induced Protein 3

Topics

• Animals
• Autoimmune Diseases (genetics, pathology)
• B-Lymphocytes (metabolism)
• DNA-Binding Proteins
• Genetic Predisposition to Disease
• Humans
• Inflammation (genetics)
• Intestinal Mucosa (metabolism, pathology)
• Intracellular Signaling Peptides and Proteins (genetics)
• Nuclear Proteins (genetics)
• Polymorphism, Single Nucleotide
• Tumor Necrosis Factor alpha-Induced Protein 3