1. Cleavage by MALT1 induces cytosolic release of A20
- Author
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Malinverni, Claire, Unterreiner, Adeline, Staal, Jens, Demeyer, Annelies, Galaup, Marion, Luyten, Marcel, Beyaert, Rudi, and Bornancin, Frédéric
- Subjects
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PROTEOLYSIS , *ARGININE , *CYTOSOL , *UBIQUITIN , *CELLULAR signal transduction , *CELL receptors , *MUCOSA-associated lymphoid tissue lymphoma - Abstract
Abstract: The MALT1 paracaspase has arginine-directed proteolytic activity. A20 is a dual ubiquitin-editing enzyme involved in termination of NF-κB signaling. Upon T- or B-cell receptor engagement human (h) A20 is cleaved by MALT1 after arginine 439, yielding an N-terminal fragment (hA20p50) and a C-terminal one (hA20p37). The hA20p50 fragment has never been detected directly, thus limiting insight into the functional consequences of MALT1-mediated cleavage of A20. Here, various antibodies were tested, including newly generated hA20p50 and hA20p37 specific antibodies, leading to detection of the hA20p50 fragment produced after MALT1-mediated cleavage of ectopically expressed as well as endogenous A20 proteins. The properties of both A20 fragments, generated upon co-expression with a constitutively active MALT1 protein, were further studied by sub-cellular fractionation and fluorescence microscopy. In contrast to full-length A20 which is particulate and insoluble, we found hA20p50 to be soluble and readily released into the cytosol whereas hA20p37 was partially soluble, thus suggesting loss of compartmentalization as a possible mechanism for MALT1-mediated dampening of A20 function. [ABSTRACT FROM AUTHOR]
- Published
- 2010
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