Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Sci. Signal., 26 February 2008
Vol. 1, Issue 8, p. ec69
[DOI: 10.1126/stke.18ec69]

EDITORS' CHOICE

Immunology Looks Like a Protease, Walks Like a Protease...

L. Bryan Ray

Science, Science Signaling, AAAS, Washington, DC 20005, USA

The protein MALT1 (for mucosa-associated lymphoid tissue lymphoma translocation 1) has sequence similarity to proteases, but its best-characterized signaling role is not derived from protease activity. MALT1 is a component of the signalosome protein complex that transmits signals from the T cell and B cell antigen receptors to the transcriptional regulator NF-{kappa}B. In the signalosome, MALT1’s presumed protease activity appears not to be essential to activation of NF-{kappa}B, and MALT1 instead contributes to ubiquitination of I{kappa}B kinase {gamma} (IKK{gamma}). Two papers now show that the protease catalytic domain is indeed put to good use during T cell activation. Rebeaud et al. show that the adaptor protein Bcl-10 (also part of the signalosome) is a target for MALT1-mediated proteolysis. They went on to develop an inhibitor of MALT1 protease activity and showed that although NF-{kappa}B through the T cell receptor did not require MALT1 activity, the protease was necessary for optimal activation of NF-{kappa}B. Furthermore, depletion of MALT1 or Bcl-10 with siRNA showed that cleavage of Bcl-10 was required for optimal adhesion of activated T cells to fibronectin. Coornaert et al. discovered another target of MALT1-mediated proteolysis--the A20 protein, an inhibitor of NF-{kappa}B signaling pathway that they found was also recruited to the signalosome. A20 has deubiquitinase activity, and one of its targets is IKK{gamma}. The MALT-1-mediated cleavage of A20 may inhibit deubiquitination of IKK{gamma} by lopping off a binding domain of A20 that interacts with IKK{gamma}. Thus, MALT1’s protease activity apparently has at least two effects on immune responses to antigen--inactivation of an inhibitor of the NF-{kappa}B signaling pathway and facilitation of integrin-mediated adhesion. McAllister-Lucas and Lucas provide background and commentary.

F. Rebeaud, S. Hailfinger, A. Posevitz-Fejfar, M. Tapernoux, R. Moser, D. Rueda, O. Gaide, M. Guzzardi, E. M. Iancu, N. Rufer, N. Fasel, M. Thome, The proteolytic activity of the paracaspase MALT1 is key in T cell activation. Nat. Immunol. 9, 272-281 (2008). [PubMed]

B. Coornaert, M. Baens, K. Heyninck, T. Bekaert, M. Haegman, J. Staal, L. Sun, Z. J. Chen, P. Marynen, R. Beyaert, T cell antigen receptor stimulation induces MALT1 paracaspase-mediated cleavage of the NF-{kappa}B inhibitor A20. Nat. Immunol. 9, 263-271 (2008). [PubMed]

L. M. McAllister-Lucas, P. C. Lucas, Finally, MALT1 is a protease! Nat. Immunol. 9, 231-233 (2008). [PubMed]

Citation: L. B. Ray, Looks Like a Protease, Walks Like a Protease... Sci. Signal. 1, ec69 (2008).


To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882