title: MALT1 contains nuclear export signals and regulates cytoplasmic localization of BCL10.
abstract: MALT1, BCL10 (B-cell lymphoma 10), and API2 (apoptosis inhibitor 2)-MALT1 are key molecules in mucosa-associated lymphoid tissue (MALT) lymphomagenesis. We previously reported that MALT1 and API2-MALT1 were localized only in cytoplasm, where we suggested that both molecules were likely to be active. In the study presented here, we further examined the localization-determining region by generating various mutants and were able to demonstrate that there were nuclear export signal (NES)-containing domains in the MALT1 C-terminal region. The use of leptomycin B, an NES-specific inhibitor, demonstrated that both MALT1 and API2-MALT1 were predominantly retained in the nuclei, indicating that these molecules were shuttling between nucleus and cytoplasm in an NES-dependent manner. It was also found that MALT1 was involved in the nuclear export of BCL10, which is originally localized in both nucleus and cytoplasm. These results correlate well with the nuclear BCL10 expression pattern in both t(1;14) and t(11;18) MALT lymphomas. The nucleocytoplasmic shuttling of MALT1 and BCL10 complex may indicate that these molecules are involved not only in the nuclear factor kappaB (NF-kappaB) pathway but also in other biologic functions in lymphocytes.
authors.affiliation: Division of Molecular Medicine, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya 464-8681, Japan.
authors.forename: Masao
authors.initials: M
authors.lastname: Nakagawa
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Hosokawa
authors.forename: Masakatsu
authors.initials: M
authors.lastname: Yonezumi
authors.forename: Koh
authors.initials: K
authors.lastname: Izumiyama
authors.forename: Ritsuro
authors.initials: R
authors.lastname: Suzuki
authors.forename: Shinobu
authors.initials: S
authors.lastname: Tsuzuki
authors.forename: Masahiro
authors.initials: M
authors.lastname: Asaka
authors.forename: Masao
authors.initials: M
authors.lastname: Seto
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D000074018:B-Cell CLL-Lymphoma 10 Protein; D019556:COS Cells; D020169:Caspases; D002522:Chlorocebus aethiops; D003593:Cytoplasm / Q000378:metabolism*; D006801:Humans; D018442:Lymphoma, B-Cell, Marginal Zone / Q000235:genetics / Q000378:metabolism*; D000074884:Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein; D016328:NF-kappa B / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D049790:Nuclear Export Signals / Q000502:physiology*; D021381:Protein Transport; D017386:Sequence Homology, Amino Acid
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D000074018:B-Cell CLL-Lymphoma 10 Protein; C118591:BCL10 protein, human; D016328:NF-kappa B; D009363:Neoplasm Proteins; D049790:Nuclear Export Signals; D020169:Caspases; C400109:MALT1 protein, human; D000074884:Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein