Tumor necrosis factor receptor-associated factor 3 (TRAF3), an intracellular signal transducer, is identified as an important component of Toll-like receptors and RIG-I-like receptors induced type I interferon (IFN) signaling pathways. Previous studies have clarified TRAF3 function in mammals, but little is known about the role of TRAF3 in ducks. Here, we cloned and characterized the full-lengt...

Tumor necrosis factor receptor-associated factor 3 (TRAF3) is a crucial regulator that suppresses c-Jun N-terminal kinase and non-canonical nuclear factor-kB signaling, but facilitates type I interferon production. To determine TRAF3 function in innate immune responses among birds, particularly chicken, we cloned and characterized the chicken TRAF3 gene (chTRAF3) and detected its tissue express...

Non-Hodgkin’s lymphoma is the leading cause of hematologic cancer in adults and the 7 leading cause of death in the United States. Importantly, B-cell lymphomas account for 85% of Non-Hodgkin’s Lymphoma and 90% of lymphomas altogether. Therefore, it is necessary to further delineate the molecular mechanisms of B-cell lymphomagenesis in order to develop novel therapeutic treatments for the disea...

CD27 belongs to TNF receptor family, and it is unique in this family for its disulfide-linked homodimerization of 55-kDa monomers. In the present study we demonstrate that overexpression of CD27 in 293 cells induces a low level of NF-kappaB activation, and the ligation of the receptor by its corresponding ligand (CD70) augments this signal dramatically. Either TNF receptor-associated factor-2 (...

The interleukin 1 receptor (IL-1R) and the Toll-like receptors (TLRs) are highly homologous innate immune receptors that provide the first line of defense against infection. We show that IL-1R type I (IL-1RI) is essential for TLR9-dependent activation of tumor necrosis factor receptor-associated factor 3 (TRAF3) and for production of the antiinflammatory cytokines IL-10 and type I interferon (I...

NF-κB, a central proinflammatory regulator, gets activated by TNF receptor–associated factors (TRAFs). But He et al. (page 2413) now report that one TRAF family member (TRAF3) instead negatively regulates an alternative NF-κB activation pathway. Classical activation of NF-κB occurs by TRAF-controlled degradation of cytoplasmic inhibitory binding proteins, which leads to nuclear accumulation of ...

Abstract Toll-like receptors (TLRs) are pattern recognition that bridge the innate and adaptive immune system critical for host defense. TLR signaling to B cells is important in normal immunity, but also implicated autoimmune disease cell lymphomas (BCL). Most studies focus on role of TLRs myeloid populations. However, express most highly responsive ligands, yet TLR-mediated pathways understudi...

Severe acute respiratory syndrome coronavirus (SARS-CoV) papain-like protease (PLPro) reportedly inhibits the production of type I interferons (IFNs) and pro-inflammatory cytokines in Toll-like receptor 3 (TLR3) and retinoic acid-inducible gene 1 (RIG-I) pathways. The study investigated the inhibitory effect and its antagonistic mechanism of SARS-CoV PLPro on TLR7-mediated cytokine production. ...

BACKGROUND Identification of novel genetic risk factors is imperative for a better understanding of B lymphomagenesis and for the development of novel therapeutic strategies. TRAF3, a critical regulator of B cell survival, was recently recognized as a tumor suppressor gene in B lymphocytes. The present study aimed to identify novel oncogenes involved in malignant transformation of TRAF3-deficie...

The downstream of kinase (DOK) family of adaptors is generally involved in the negative regulation of signaling pathways. DOK1, 2, and 3 were shown to attenuate TLR4 signaling by inhibiting Ras-ERK activation. In this study, we elucidated a novel role for DOK3 in IFN-β production. Macrophages lacking DOK3 were impaired in IFN-β synthesis upon influenza virus infection or polyinosinic-polyribocy...