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Stability and subcellular localization of API2-MALT1 chimeric protein involved in t(11;18) (q21;q21) MALT lymphoma

Abstract

t(11; 18) (q21; q21) is a chromosomal aberration specific to low-grade mucosa-associated lymphoid tissue (MALT) lymphoma, and generates the chimeric product apoptosis inhibitor 2 (API2)-MALT1, which has been suggested to play an important role in MALT lymphomagenesis. However, little is known about the characteristics of API2, MALT1, and API2-MALT1 proteins. We therefore investigated the subcellular localization and stability of these products. API2 was localized in the nucleus and the cytoplasm, and MALT1 and API2-MALT1 in the cytoplasm only. Western blot analysis showed that the products of API2 and MALT1 were unstable, while the API2-MALT1 product was stable. The API2 deletion mutants at the end of the C-terminal and the MALT1 deletion mutants at the end of the N-terminal were stable compared with the full-length products. These results indicate that the domains responsible for protein instability are located in the end of the C-terminal of API2 and in that of the N-terminal of MALT1, and also that API2-MALT1 became stable because it lacks these domains. It has been suggested that NF-κB activation plays an important role in the tumorigenesis of MALT lymphoma. Our findings further suggest that the stabilized expression of API2-MALT1 products may continuously stimulate the NF-κB activating pathway, thus leading to MALT lymphomagenesis.

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References

  • Akagi T, Motegi M, Tamura A, Suzuki R, Hosokawa Y, Suzuki H, Ota H, Nakamura S, Morishima Y, Taniwaki M and Seto M . (1999). Oncogene, 18, 5785–5794.

  • Baens M, Maes B, Steyls A, Geboes K, Marynen P and Wolf-Peeters CD . (2000). Am. J. Pathol., 156, 1433–1439.

  • Barkett M and Gilmore TD . (1999). Oncogene, 18, 6910–6924.

  • Deveraux QL and Reed JC . (1999). Genes Dev., 13, 239–252.

  • Dierlamm J, Baens M, Wlodarska I, Stefanova-Ouzounova M, Hernandez JM, Hossfeld DK, Wolf-Peeters CD, Hagemeijer A, Berghe HV and Marynen P . (1999). Blood, 93, 3601–3609.

  • Fang S, Jensen JP, Ludwig RL, Vousden KH and Weissman AM . (2000). J. Biol. Chem., 275, 8945–8951.

  • Hozak RR, Manji GA and Friesen PD . (2000). Mol. Cell. Biol., 20, 1877–1885.

  • Huang H, Joazeiro CAP, Bonfoco E, Kamada S, Leverson JD and Hunter T . (2000). J. Biol. Chem., 275, 26661–26664.

  • Inagaki H, Okabe M, Seto M, Nakamura S, Ueda R and Eimoto T . (2001). Am. J. Pathol., 158, 699–706.

  • Isaacson PG . (1999). Semin. Hematol., 36, 139–147.

  • Isaacson PG and Spencer J . (1987). Histopathology, 11, 445–462.

  • Kalla J, Stilgenbauer S, Schaffner C, Wolf S, Ott G, Greiner A, Rosenwald A, Dohner H, Muller-Hermelink HK and Lichter P . (2000). Leukemia, 14, 1967–1974.

  • Kiyono T, Hiraiwa A, Ishii S, Takahashi T and Ishibashi M . (1994). J. Virol., 68, 4656–4661.

  • Lucas PC, Yonezumi M, Inohara N, McAllister-Lucas LM, Abazeed ME, Chen FF, Yamaoka S, Seto M and Nunez G . (2001). J. Biol. Chem., 276, 19012–19019.

  • McAllister-Lucas LM, Inohara N, Lucas PC, Ruland J, Benito A, Li Q, Chen S, Chen FF, Yamaoka S, Verma IM, Mak TW and Nunez G . (2001). J. Biol. Chem., 276, 30589–30597.

  • Morgan JA, Yin Y, Borowsky AD, Kuo F, Nourmand N, Koontz JI, Reynolds C, Soreng L, Griffin CA, Graeme-Cook F, Harris NL, Weisenburger D, Pinkus GS, Fletcher JA and Sklar J . (1999). Cancer Res., 59, 6205–6213.

  • Motegi M, Yonezumi M, Suzuki H, Suzuki R, Hosokawa Y, Hosaka S, Kodera Y, Morishima Y, Nakamura S and Seto M . (2000). Am. J. Pathol., 156, 807–812.

  • Ott G, Katzenberger T, Greiner A, Kalla J, Rosenwald A, Heinrich U, Ott MM and Muller-Hermelink HK . (1997). Cancer Res., 57, 3944–3948.

  • Palacios R and Steinmetz M . (1985). Cell, 41, 727–734.

  • Remstein ED, James CD and Kurtin PJ . (2000). Am. J. Pathol., 156, 1183–1188.

  • Roy N, Deveraux QL, Takahashi R, Salvesen GS and Reed JC . (1997). EMBO J., 16, 6914–6925.

  • Suzuki H, Motegi M, Akagi T, Hosokawa Y and Seto M . (1999). Blood, 94, 3270–3271.

  • Uren AG, O'Rourke K, Aravind L, Pisabarro MT, Seshagiri S, Koonin EV and Dixit VM . (2000). Mol. Cell., 6, 961–967.

  • Willis TG, Jadayel DM, Du MQ, Peng H, Perry AR, Abdul-Rauf M, Price H, Karran L, Majekodunmi O, Wlodarska I, Pan L, Crook T, Hamoudi R, Issacson PG and Dyer MJ . (1999). Cell, 96, 35–45.

  • Yang Y, Fang S, Jensen JP, Weissman AM and Ashwell JD . (2000). Science, 288, 874–877.

  • Yonezumi M, Suzuki R, Suzuki H, Yoshino T, Oshima K, Hosokawa Y, Asaka M, Morishima Y and Seto M . (2001). Br. J. Haematol., 115, 588–594.

  • Zhang Q, Siebert R, Yan M, Hinzmann B, Cui X, Xue L, Rakestraw KM, Naeve CW, Beckmann G, Weisenburger DD, Sanger WG, Nowotny H, Vesely M, Callet-Bauchu E, Salles G, Dixit VM, Rosenthal A, Schlegelberger B and Morris SW . (1999). Nat. Genet., 22, 63–68.

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Correspondence to Masao Seto.

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Izumiyama, K., Nakagawa, M., Yonezumi, M. et al. Stability and subcellular localization of API2-MALT1 chimeric protein involved in t(11;18) (q21;q21) MALT lymphoma. Oncogene 22, 8085–8092 (2003). https://doi.org/10.1038/sj.onc.1207002

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