Accumulation of BCL10 at the perinuclear region is required for the BCL10-mediated nuclear factor-kappa B activation.

摘要

OBJECTIVES: The dysregulated overexpression of BCL10 that results from a specific chromosomal translocation t(1;14)(p22;q32) in mucosa-associated lymphoid tissue lymphoma has been shown to activate nuclear factor (NF)-kappaB, which may promote growth and survival in tumor cells. Accordingly, the molecular mechanisms underlying NF-kappaB activation may be responsible for lymphomagenesis. The aim of this study was to determine the molecular mechanisms underlying NF-kappaB activation by BCL10 overexpression. METHODS: HeLa or COS-1 cells were transfected with BCL10, intracellular localization of BCL10 and the activation of NF-kappaB were analyzed. RESULTS: BCL10 expressed at a high level exhibited a filamentous distribution at the perinuclear region, whereas BCL10 at a low level of expression displayed a diffuse cytoplasmic distribution. Furthermore, the BCL10-mediated NF-kappaB activation was efficiently inhibited by a Ca2+ chelating agent or a Ca2+ channel blocker. We also found that amino acids (107-119) of BCL10 are required for the formation of filamentous structures at the perinuclear region and NF-kappaB activation. CONCLUSION: These findings suggest that the filamentous pattern of overexpressed BCL10 at the perinuclear region adjacent to the endoplasmic reticulum is important for the BCL10-mediated NF-kappaB activation.