T. Yoneda et al., Regulatory mechanisms of TRAF2-mediated signal transduction by Bcl10, a MALT lymphoma-associated protein, J BIOL CHEM, 275(15), 2000, pp. 11114-11120
To elucidate the function of Bcl10, recently cloned as an apoptosis-associa
ted gene mutated in MALT lymphoma, we identified its binding partner TRAF2,
which mediates signaling via tumor necrosis factor receptors, In mammalian
cells, low levels of Bcl10 expression promoted the binding of TRAF2 and c-
IAPs, Conversely, excessive expression inhibited complex formation. Overexp
ressed Bcl10 reduced c-Jun N-terminal kinase activation and induced nuclear
factor kappa B activation downstream of TRAF2, To determine whether overex
pression of Bcl10 could perturb the regulation of apoptosis in vivo, we gen
erated Bcl10 transgenic mice. In these transgenic mice, atrophy of the thym
us and spleen was observed at postnatal stages. The morphological changes i
n these tissues were caused by acceleration of apoptosis in T cells and B c
ells. The phenotype of Bcl10 transgenic mice was similar to that of TRAF2-d
eficient mice reported previously, indicating that excessive expression of
Bcl10 might deplete the TRAF2 function. in contrast, in the other organs su
ch as the brain, where Bcl10 was expressed at high levels, no apoptosis was
detected, The altered sensitivities to overexpressed Bcl10 may have been d
ue to differences in signal responses to Bcl10 among cell types. Thus, Bcl1
0 was suggested to play crucial roles in the modulation of apoptosis associ
ated with TRAF2.