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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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IMMUNOBIOLOGY

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

From the Division of Molecular Medicine, Aichi Cancer Center Research Institute, Chikusa-ku, Nagoya, Japan; the Department of Gastroenterology and Hematology, Hokkaido University Graduate School of Medicine, Kita-ku, Sapporo, Japan; and the Japan Biological Informatics Consortium, Koto-ku, Tokyo, Japan.

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 {kappa}B (NF-{kappa}B) pathway but also in other biologic functions in lymphocytes.


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