Auto-ubiquitination-induced degradation of MALT1-API2 prevents BCL10 destabilization in t(11;18)(q21;q21)-positive MALT lymphoma.
The translocation t(11;18)(q21;q21) is the most frequent chromosomal aberration associated with MALT lymphoma and results in constitutive NF-kappaB 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.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 (approximately 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.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.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Cell Line, Cell Nucleus, Chromosomes, Human, Pair 11, Chromosomes, Human, Pair 18, Humans, Hydrolysis, Lymphoma, B-Cell, Marginal Zone, Oncogene Proteins, Fusion, Proteasome Endopeptidase Complex, Reverse Transcriptase Polymerase Chain Reaction, Translocation, Genetic, Ubiquitination
Adaptor Proteins, Signal Transducing, Cell Line, Cell Nucleus, Chromosomes, Human, Pair 11, Chromosomes, Human, Pair 18, Humans, Hydrolysis, Lymphoma, B-Cell, Marginal Zone, Oncogene Proteins, Fusion, Proteasome Endopeptidase Complex, Reverse Transcriptase Polymerase Chain Reaction, Translocation, Genetic, Ubiquitination
PLoS ONE
Date: Mar. 13, 2009
PubMed ID: 19279678
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