Regulatory mechanisms of TRAF2-mediated signal transduction by Bcl10, a MALT lymphoma-associated protein

Citation
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
Citations number
21
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biochemistry & Biophysics
Journal title
JOURNAL OF BIOLOGICAL CHEMISTRY
ISSN journal
0021-9258 → ACNP
Volume
275
Issue
15
Year of publication
2000
Pages
11114 - 11120
Database
ISI
SICI code
0021-9258(20000414)275:15<11114:RMOTST>2.0.ZU;2-J
Abstract
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.