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Gene Review

MALT1  -  MALT1 paracaspase

Homo sapiens

Synonyms: IMD12, MALT lymphoma-associated translocation, MLT, MLT1, Mucosa-associated lymphoid tissue lymphoma translocation protein 1, ...
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Disease relevance of MALT1


High impact information on MALT1


Biological context of MALT1


Anatomical context of MALT1

  • 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 [10].
  • Among a total of 66 cases, t(14;18)(q32;q21) involving IGH and MALT1 was detected in MALT lymphomas of the liver (4 of 4), skin (3 of 11), ocular adnexa (3 of 8), and salivary gland (2 of 11), but did not occur in MALT lymphomas of the stomach (n = 10), intestine (n = 9), lung (n = 7), thyroid (n = 4), or breast (n = 2) [2].
  • This study identifies IGH as a new translocation partner of MALT1 in MALT lymphomas, which tend to arise frequently at sites other than the gastrointestinal tract and lung [2].
  • In normal B-cell follicles, both MALT1 and BCL10 were expressed predominantly in the cytoplasm, high in centroblasts, moderate in centrocytes and weak/negative in mantle zone B-cells [13].
  • The CARD domain protein BCL10 and paracaspase MALT1 are essential for the activation of IkappaB kinase (IKK) and NF-kappaB in response to T cell receptor (TCR) stimulation [6].

Associations of MALT1 with chemical compounds

  • 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 [10].
  • The sequence of this gene indicates the presence of two immunoglobulin-like C2 domains and a region of partial homology to caspases, suggesting a possible role for MALT1 in the regulation of apoptosis [14].
  • Expression of API2-MALT1 fusion transcripts was detected by reverse transcription-polymerase chain reaction analysis using formalin-fixed, paraffin-embedded tissue [15].
  • RNA interference against MALT1 markedly reduced the level of NF-kappaB activation stimulated by lipopolysaccharide (LPS) in macrophages, which suggests that MALT1 plays a major role in the LPS/TLR4 pathway [16].
  • Finally, M. isabellina improved its degradation potential in Tartaric Acid (TA) medium relative to GS and Malt Extract (ME) media [17].

Physical interactions of MALT1


Regulatory relationships of MALT1

  • MALT1 contains nuclear export signals and regulates cytoplasmic localization of BCL10 [10].
  • Expression of a MALT1 deletion mutant containing only the N-terminal death domain and the two Ig-like domains completely blocked CD3/CD28 costimulation-induced, but not tumor necrosis factor-alpha-induced, NF-kappaB activation [12].
  • API2-MALT1 fusion protein induces transcriptional activation of the API2 gene through NF-kappaB binding elements: evidence for a positive feed-back loop pathway resulting in unremitting NF-kappaB activation [19].

Other interactions of MALT1

  • In this study, we show that MALT1 is recruited into the lipid rafts of the immunological synapse following activation of the TCR and the CD28 coreceptor (CD3/CD28 costimulation) [12].
  • Subsequent fluorescence in situ hybridization (FISH) studies disclosed that the immunoglobulin heavy-chain locus (IGH) and the MALT1 gene were rearranged by this translocation [2].
  • Moreover, our findings suggest that genomic gain of genes that modulate NFkappaB activation, such as MALT1, TRAF2 and CARD9, may play a role in the pathogenesis of the translocation-negative MALT lymphoma [20].
  • This is the first time that MALT1 and BCL2 have been shown to be overexpressed and amplified in MM [21].
  • MALT1/paracaspase is a signaling component downstream of CARMA1 and mediates T cell receptor-induced NF-kappaB activation [12].

Analytical, diagnostic and therapeutic context of MALT1

  • This study further supports the close interaction between the MALT1 and BCL10 proteins in the pathogenesis of MALT lymphomas and may indicate that BCL10 immunohistochemistry is a simple technique to identify those MALT lymphoma cases with an underlying genetic aberration [22].
  • Genetic and biochemical experiments identified BCL10 and MALT1 as central components of an oligomerization-ubiquitinylation-phosphorylation cascade that activates the transcription factor NF-kappaB in response to antigen receptor ligation [23].
  • Thus, the RT-PCR assay used here should serve as an effective molecular tool for understanding molecular pathogenesis and the clinical significance of API2-MALT1 for MALT lymphomas [24].
  • Real-time polymerase chain reaction (PCR) was used to examine number of API2-MALT1 copies in clinical samples for further investigation of the pathophysiology of MALT lymphoma [25].
  • We determined the API2/MALT1 fusion transcript in 2 cases by Northern blot analysis and also showed that MALT1 mRNA is constitutively expressed in a variety of human tissues [26].


  1. cIAP2 is a ubiquitin protein ligase for BCL10 and is dysregulated in mucosa-associated lymphoid tissue lymphomas. Hu, S., Du, M.Q., Park, S.M., Alcivar, A., Qu, L., Gupta, S., Tang, J., Baens, M., Ye, H., Lee, T.H., Marynen, P., Riley, J.L., Yang, X. J. Clin. Invest. (2006) [Pubmed]
  2. T(14;18)(q32;q21) involving IGH and MALT1 is a frequent chromosomal aberration in MALT lymphoma. Streubel, B., Lamprecht, A., Dierlamm, J., Cerroni, L., Stolte, M., Ott, G., Raderer, M., Chott, A. Blood (2003) [Pubmed]
  3. API2-MALT1 fusion defines a distinctive clinicopathologic subtype in pulmonary extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue. Okabe, M., Inagaki, H., Ohshima, K., Yoshino, T., Li, C., Eimoto, T., Ueda, R., Nakamura, S. Am. J. Pathol. (2003) [Pubmed]
  4. MALT1 is deregulated by both chromosomal translocation and amplification in B-cell non-Hodgkin lymphoma. Sanchez-Izquierdo, D., Buchonnet, G., Siebert, R., Gascoyne, R.D., Climent, J., Karran, L., Marin, M., Blesa, D., Horsman, D., Rosenwald, A., Staudt, L.M., Albertson, D.G., Du, M.Q., Ye, H., Marynen, P., Garcia-Conde, J., Pinkel, D., Dyer, M.J., Martinez-Climent, J.A. Blood (2003) [Pubmed]
  5. Clinical features and prognosis of gastric MALT lymphoma with special reference to responsiveness to H. pylori eradication and API2-MALT1 status. Nakamura, T., Seto, M., Tajika, M., Kawai, H., Yokoi, T., Yatabe, Y., Nakamura, S. Am. J. Gastroenterol. (2008) [Pubmed]
  6. The TRAF6 ubiquitin ligase and TAK1 kinase mediate IKK activation by BCL10 and MALT1 in T lymphocytes. Sun, L., Deng, L., Ea, C.K., Xia, Z.P., Chen, Z.J. Mol. Cell (2004) [Pubmed]
  7. Delving deeper into MALT lymphoma biology. Bertoni, F., Zucca, E. J. Clin. Invest. (2006) [Pubmed]
  8. CARMA3/Bcl10/MALT1-dependent NF-{kappa}B activation mediates angiotensin II-responsive inflammatory signaling in nonimmune cells. McAllister-Lucas, L.M., Ruland, J., Siu, K., Jin, X., Gu, S., Kim, D.S., Kuffa, P., Kohrt, D., Mak, T.W., Nu??ez, G., Lucas, P.C. Proc. Natl. Acad. Sci. U.S.A. (2007) [Pubmed]
  9. Bcl10 and Malt1 control lysophosphatidic acid-induced NF-{kappa}B activation and cytokine production. Klemm, S., Zimmermann, S., Peschel, C., Mak, T.W., Ruland, J. Proc. Natl. Acad. Sci. U.S.A. (2007) [Pubmed]
  10. MALT1 contains nuclear export signals and regulates cytoplasmic localization of BCL10. Nakagawa, M., Hosokawa, Y., Yonezumi, M., Izumiyama, K., Suzuki, R., Tsuzuki, S., Asaka, M., Seto, M. Blood (2005) [Pubmed]
  11. Bcl10 and MALT1, independent targets of chromosomal translocation in malt lymphoma, cooperate in a novel NF-kappa B signaling pathway. Lucas, P.C., Yonezumi, M., Inohara, N., McAllister-Lucas, L.M., Abazeed, M.E., Chen, F.F., Yamaoka, S., Seto, M., Nunez, G. J. Biol. Chem. (2001) [Pubmed]
  12. MALT1/paracaspase is a signaling component downstream of CARMA1 and mediates T cell receptor-induced NF-kappaB activation. Che, T., You, Y., Wang, D., Tanner, M.J., Dixit, V.M., Lin, X. J. Biol. Chem. (2004) [Pubmed]
  13. MALT lymphoma with t(14;18)(q32;q21)/IGH-MALT1 is characterized by strong cytoplasmic MALT1 and BCL10 expression. Ye, H., Gong, L., Liu, H., Hamoudi, R.A., Shirali, S., Ho, L., Chott, A., Streubel, B., Siebert, R., Gesk, S., Martin-Subero, J.I., Radford, J.A., Banerjee, S., Nicholson, A.G., Ranaldi, R., Remstein, E.D., Gao, Z., Zheng, J., Isaacson, P.G., Dogan, A., Du, M.Q. J. Pathol. (2005) [Pubmed]
  14. Breakpoints of the t(11;18)(q21;q21) in mucosa-associated lymphoid tissue (MALT) lymphoma lie within or near the previously undescribed gene MALT1 in chromosome 18. Morgan, J.A., Yin, Y., Borowsky, A.D., Kuo, F., Nourmand, N., Koontz, J.I., Reynolds, C., Soreng, L., Griffin, C.A., Graeme-Cook, F., Harris, N.L., Weisenburger, D., Pinkus, G.S., Fletcher, J.A., Sklar, J. Cancer Res. (1999) [Pubmed]
  15. Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) arising in the small intestine with monoclonal cryoglobulinemia. Saito, T., Tamaru, J., Kishi, H., Kayao, J., Kuzuu, Y., Wakita, H., Adachi, A., Itoyama, S., Mikata, I. Pathol. Int. (2004) [Pubmed]
  16. The IRAK-1-BCL10-MALT1-TRAF6-TAK1 cascade mediates signaling to NF-kappaB from Toll-like receptor 4. Dong, W., Liu, Y., Peng, J., Chen, L., Zou, T., Xiao, H., Liu, Z., Li, W., Bu, Y., Qi, Y. J. Biol. Chem. (2006) [Pubmed]
  17. Fungal bioconversion of 2,4-dichlorophenoxyacetic acid (2,4-D) and 2,4-dichlorophenol (2,4-DCP). Vroumsia, T., Steiman, R., Seigle-Murandi, F., Benoit-Guyod, J.L. Chemosphere (2005) [Pubmed]
  18. Marginal-zone B-cell lymphoma of extranodal mucosa-associated lymphoid tissue type: molecular genetics provides new insights into pathogenesis. Vega, F., Medeiros, L.J. Advances in anatomic pathology. (2001) [Pubmed]
  19. API2-MALT1 fusion protein induces transcriptional activation of the API2 gene through NF-kappaB binding elements: evidence for a positive feed-back loop pathway resulting in unremitting NF-kappaB activation. Hosokawa, Y., Suzuki, H., Nakagawa, M., Lee, T.H., Seto, M. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  20. Distinct comparative genomic hybridisation profiles in gastric mucosa-associated lymphoid tissue lymphomas with and without t(11;18)(q21;q21). Zhou, Y., Ye, H., Martin-Subero, J.I., Hamoudi, R., Lu, Y.J., Wang, R., Siebert, R., Shipley, J., Isaacson, P.G., Dogan, A., Du, M.Q. Br. J. Haematol. (2006) [Pubmed]
  21. Identification of overexpressed genes in frequently gained/amplified chromosome regions in multiple myeloma. Largo, C., Alvarez, S., Saez, B., Blesa, D., Martin-Subero, J.I., González-García, I., Brieva, J.A., Dopazo, J., Siebert, R., Calasanz, M.J., Cigudosa, J.C. Haematologica (2006) [Pubmed]
  22. MALT1 and BCL10 aberrations in MALT lymphomas and their effect on the expression of BCL10 in the tumour cells. Sagaert, X., Laurent, M., Baens, M., Wlodarska, I., De Wolf-Peeters, C. Mod. Pathol. (2006) [Pubmed]
  23. The Bcl10/Malt1 signaling pathway as a drug target in lymphoma. Jost, P., Peschel, C., Ruland, J. Current drug targets. (2006) [Pubmed]
  24. API2-MALT1 chimeric transcripts involved in mucosa-associated lymphoid tissue type lymphoma predict heterogeneous products. Motegi, M., Yonezumi, M., Suzuki, H., Suzuki, R., Hosokawa, Y., Hosaka, S., Kodera, Y., Morishima, Y., Nakamura, S., Seto, M. Am. J. Pathol. (2000) [Pubmed]
  25. Heterogeneous copy numbers of API2-MALT1 chimeric transcripts in mucosa-associated lymphoid tissue lymphoma. Suguro-Katayama, M., Suzuki, R., Kasugai, Y., Nakamura, T., Suzuki, H., Hosokawa, Y., Shiku, H., Nakamura, S., Seto, M. Leukemia (2003) [Pubmed]
  26. The API2/MALT1 fusion product may lead to germinal center B cell lymphomas by suppression of apoptosis. Stoffel, A., Le Beau, M.M. Hum. Hered. (2001) [Pubmed]
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