Signaling Human CD40 Receptor with Enhanced Differential TRAF3 Utilization by a Variant

Human CD40 Receptor with Enhanced Differential TRAF3 Utilization by a Variant

Requirement for TRAF3 in Signaling by LMP1 But Not CD40 in B Lymphocytes

CD40, a member of the tumor necrosis factor receptor family, and the Epstein-Barr virus-encoded oncoprotein latent membrane protein 1 (LMP1) share several tumor necrosis factor receptor-associated factor (TRAF) adaptor proteins for signaling. Among these, TRAF3 was the first identified to directly bind both receptors, yet its role remains a mystery. To address this, we generated B cell lines de...

Dysregulation of CD40 signaling pathways in enhanced B cell activation and autoimmunity

CD40 signals are required for productive immune responses but also play a role in autoimmune disease pathogenesis. The major goal of this research was to investigate the contribution of two receptors to the development of autoimmune disease: (1) LMP1, an oncogenic EBV-encoded mimic of CD40 and (2) a naturally-occurring polymorphism in CD40, P227A, which appears to confer LMP1-like properties to...

LMP1 protein from the Epstein-Barr virus is a structural CD40 decoy in B lymphocytes for binding to TRAF3.

Epstein-Barr virus is a human herpesvirus that causes infectious mononucleosis and lymphoproliferative malignancies. LMP1 (latent membrane protein-1), which is encoded by this virus and which is essential for transformation of B lymphocytes, acts as a constitutively active mimic of the tumor necrosis factor receptor (TNFR) CD40. LMP1 is an integral membrane protein containing six transmembrane ...

Assembly and Regulation of the CD40 Receptor Complex in Human B Cells

CD40 is a member of the tumor necrosis factor (TNF) receptor superfamily. Studies with human B cells show that the binding of CD154 (gp39, CD40L) to CD40 recruits TNF receptor- associated factor 2 (TRAF2) and TRAF3 to the receptor complex, induces the downregulation of the nonreceptor-associated TRAFs in the cell and induces an increased expression of Fas on the cell surface. Combined signaling...