How does the viral oncoprotein LMP1 utilize TRAF molecules in altering B lymphocyte function?

The tumor necrosis factor receptor (TNFR) superfamily member CD40 delivers multiple signals to B cells that play major roles in B cell survival, expansion, and differentiated functions. The EBV-encoded viral mimic of CD40, latent membrane protein 1 (LMP1) delivers strikingly similar signals to B cells, but does so in an amplified and sustained manner. This dysregulated signaling is consistent with the well-documented association of LMP1 function with human B cell lymphoma, and emerging information on the potential role of LMP1 in autoimmune disease.

In recent years, we discovered that CD40 and LMP1 use the same cytoplasmic adapter molecules (TNFR associated factors, TRAF) in unexpectedly distinct and even sharply contrasting ways. LMP1 signaling is independent of TRAF2, a major mediator of CD40 signals. Conversely, TRAF3 was revealed as a negative regulator of CD40 signaling, but a necessary positive mediator of key LMP1 signals.

Both CD40 and LMP1 also employ TRAFs 5 and 6 in B cell ... more.

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