%0 Journal Article
%T Auto-Ubiquitination-Induced Degradation of MALT1-API2 Prevents BCL10 Destabilization in t(11;18)(q21;q21)-Positive MALT Lymphoma
%A Heidi Noels
%A Riet Somers
%A Hongxiang Liu
%A Hongtao Ye
%A Ming-Qing Du
%A Christiane De Wolf-Peeters
%A Peter Marynen
%A Mathijs Baens
%J PLOS ONE
%D 2009
%I Public Library of Science (PLoS)
%R 10.1371/journal.pone.0004822
%X Background The translocation t(11;18)(q21;q21) is the most frequent chromosomal aberration associated with MALT lymphoma and results in constitutive NF-¦ĘB activity via the expression of an API2-MALT1 fusion protein. The properties of the reciprocal MALT1-API2 were never investigated as it was reported to be rarely transcribed. Principal Findings Our data indicate the presence of MALT1-API2 transcripts in the majority of t(11;18)(q21;q21)-positive MALT lymphomas. Based on the breakpoints in the MALT1 and API2 gene, the MALT1-API2 protein contains the death domain and one or both immunoglobulin-like domains of MALT1 (~90% of cases) - mediating the possible interaction with BCL10 - fused to the RING domain of API2. Here we show that this RING domain enables MALT1-API2 to function as an E3 ubiquitin ligase for BCL10, inducing its ubiquitination and proteasomal degradation in vitro. Expression of MALT1-API2 transcripts in t(11;18)(q21;q21)-positive MALT lymphomas was however not associated with a reduction of BCL10 protein levels. Conclusion As we observed MALT1-API2 to be an efficient target of its own E3 ubiquitin ligase activity, our data suggest that this inherent instability of MALT1-API2 prevents its accumulation and renders a potential effect on MALT lymphoma development via destabilization of BCL10 unlikely.
%U http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0004822