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


CONCLUSIONS
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.
Nakamura
Kyoko
K
Division of Molecular Biology, Department of Molecular and Cellular Biology, School of Life Science, Faculty of Medicine, Tottori University, Yonago, Japan.
Senda
Takao
T
Sato
Kenzo
K
Mori
Shigeo
S
Moriyama
Masatsugu
M
D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis* / Q000235:genetics; D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D000074018:B-Cell CLL-Lymphoma 10 Protein; D015153:Blotting, Western; D019556:COS Cells; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002467:Cell Nucleus / Q000378:metabolism*; D002614:Chelating Agents / Q000494:pharmacology; D002522:Chlorocebus aethiops; D003620:Dantrolene / Q000494:pharmacology; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004926:Escherichia coli / Q000235:genetics; D017353:Gene Deletion; D015972:Gene Expression Regulation, Neoplastic; D005982:Glutathione Transferase / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D007150:Immunohistochemistry; D008156:Luciferases / Q000378:metabolism; D016253:Microscopy, Immunoelectron; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D000074018:B-Cell CLL-Lymphoma 10 Protein; C118591:BCL10 protein, human; D002121:Calcium Channel Blockers; D002614:Chelating Agents; D016328:NF-kappa B; D011993:Recombinant Fusion Proteins; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; D049452:Green Fluorescent Proteins; D004533:Egtazic Acid; D008156:Luciferases; D005982:Glutathione Transferase; D003620:Dantrolene