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Blood, 15 December 2005, Vol. 106, No. 13, pp. 4210-4216.
Prepublished online as a Blood First Edition Paper on August 25, 2005; DOI 10.1182/blood-2004-12-4785.
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Submitted December 16, 2004
Accepted August 2, 2005
MALT1 contains nuclear export signals and regulates cytoplasmic localization of BCL10
Masao Nakagawa, Yoshitaka Hosokawa, Masakatsu Yonezumi, Koh Izumiyama, Ritsuro Suzuki, Shinobu Tsuzuki, Masahiro Asaka, and Masao Seto*
Division of Molecular Medicine, Aichi Cancer Center Research Institute, Nagoya, Japan; Department of Gastroenterology and Hematology, Hokkaido University Graduate School of Medicine, Sapporo, Japan; Japan Biological Informatics Consortium, Tokyo, Japan
Division of Molecular Medicine, Aichi Cancer Center Research Institute, Nagoya, Japan
Division of Molecular Medicine, Aichi Cancer Center Research Institute, Nagoya, Japan; Department of Gastroenterology and Hematology, Hokkaido University Graduate School of Medicine, Sapporo, Japan
Department of Gastroenterology and Hematology, Hokkaido University Graduate School of Medicine, Sapporo, Japan
* Corresponding author; email: mseto{at}aichi-cc.jp.
MALT1, BCL10 and API2-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 NF- B pathway but also in other biological functions in lymphocytes.
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