This hypothesis was addressed via 2 complementary approaches: (1) comparison of TRAF3-regulated activation and survival-related events with relative LMP1 expression in human BCL lines and (2) analysis of the impact upon such events in matched pairs of mouse BCL lines, both parental cells and subclones transfected with inducible LMP1, either wild-type LMP1 or a mutant LMP1 with defective TRAF3 binding.
Consistent with these findings, loss-of-function human TRAF3 mutations are common in B-cell cancers, particularly multiple myeloma and B-cell lymphoma.
We report here that CD40-induced TRAF3-dependent activation of mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) kinase 1 (MEK1) is involved in the upregulation of IL-4-driven germline C epsilon transcription in a human Burkitt's lymphoma B cell line, DG75.