TRAF1 Gene

The TRAF1 gene (TRAF1 stands for "TNF Receptor Associated Factor 1") is a protein-coding gene located on chromosome 9q33.2. The protein encoded by the TRAF1 gene is a member of the TNF receptor (TNFR) associated factor (TRAF) family. Three transcript variants have been found for this gene, encoding two different isoforms.

TRAF proteins associate with several receptors of the TNFR superfamily and mediate their signal transduction. TRAF1 protein and TRAF2 protein together form a heterodimeric complex required for TNF-alpha-mediated activation of MAPK8/JNK and NF-kappaB. This protein complex also interacts with inhibitor-of-apoptosis proteins (IAPs) to mediate TNF receptor anti-apoptotic signaling.

Recent studies have uncovered another role for TRAF1 that is independent of its role in the TNFR superfamily, namely the negative regulation of Toll-like receptor and Nod-like receptor signaling by sequestering the linear ubiquitin assembly complex LUBAC (Edilova MI et al. 2018).

TRAF1 protein expression can be induced by Epstein-Barr virus (EBV). EBV infection membrane protein 1 (LMP1) has been shown to interact with TRAF1 protein and other TRAF proteins. It is likely that this interaction links LMP1-mediated B lymphocyte transformation to signal transduction of TNFR family receptors.

TRAF1 plays a diverse role in human disease. TRAF1 is overexpressed in many B-cell cancers, and single nucleotide polymorphisms (SNPs) in TRAF1 have been associated with non-Hodgkin's lymphoma (anaplastic large cell lymphoma). Genome-wide association studies have found an association between SNPs in the 5'-untranslated region of the TRAF1 gene and increased incidence and severity of rheumatoid arthritis and other rheumatic diseases. Loss of TRAF1 in chronically stimulated CD8 T cells desensitizes the 4-1BB pathway, contributing to T cell exhaustion in chronic infections.

Diseases associated with TRAF1 include:

• Rheumatoid arthritis
• Anaplastic large cell lymphoma(CD30 Positive Anaplastic Large Cell Lymphoma) Note: Anaplastic large cell lymphoma (ALCL) is a rare form of non-Hodgkin lymphoma. The lymphoma usually involves the T cells. There are two types of ALCL: one variant that mainly affects the skin (cutaneous ALCL), and a second non-dermatotropic variant (systemic ALCL).

1. Edilova MI et al (2018) TRAF1 Signaling in Human Health and Disease. Front Immunol 9:2969.

2. Redler S et al (2010) The TRAF1/C5 locus confers risk for familial and severe alopecia areata. Br J Dermatol 162:866-869.