MALT1 contains nuclear export signals and regulates cytoplasmic localization of BCL10

• Published in: Blood Vol. 106; no. 13; pp. 4210 - 4216
• Main Authors: Nakagawa, Masao, Hosokawa, Yoshitaka, Yonezumi, Masakatsu, Izumiyama, Koh, Suzuki, Ritsuro, Tsuzuki, Shinobu, Asaka, Masahiro, Seto, Masao
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 15-12-2005; The Americain Society of Hematology
• Subjects: Adaptor Proteins, Signal Transducing - metabolism; Amino Acid Sequence; Animals; Apoptosis Regulatory Proteins - genetics; Apoptosis Regulatory Proteins - metabolism; B-Cell CLL-Lymphoma 10 Protein; Biological and medical sciences; Caspases; Chlorocebus aethiops; COS Cells; Cytoplasm - metabolism; Hematologic and hematopoietic diseases; Humans; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymphoma, B-Cell, Marginal Zone - genetics; Lymphoma, B-Cell, Marginal Zone - metabolism; Medical sciences; Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein; Neoplasm Proteins - genetics; Neoplasm Proteins - metabolism; NF-kappa B - metabolism; Nuclear Export Signals - physiology; Protein Transport; Sequence Homology, Amino Acid; Chromosomal aberration; Human; Nuclear Export Signal; Malignant hemopathy; Non Hodgkin lymphoma; Carcinogenesis; Abnormal chromosome E18; MALT lymphoma; Lymphoproliferative syndrome; Abnormal chromosome A1; Abnormal chromosome D14; Abnormal chromosome; Abnormal chromosome C11; Localization; Fusion protein; Cytoplasm; Hybrid gene; Chromosome translocation
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2004-12-4785

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 κB (NF-κB) pathway but also in other biologic functions in lymphocytes.