1. Cleavage by MALT1 induces cytosolic release of A20.
- Author
-
Malinverni C, Unterreiner A, Staal J, Demeyer A, Galaup M, Luyten M, Beyaert R, and Bornancin F
- Subjects
- Cell Line, Tumor, DNA-Binding Proteins, Humans, Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein, Peptide Fragments analysis, Peptide Fragments metabolism, Protein Transport, Tumor Necrosis Factor alpha-Induced Protein 3, Caspases metabolism, Cytosol enzymology, Intracellular Signaling Peptides and Proteins metabolism, Neoplasm Proteins metabolism, Nuclear Proteins metabolism
- 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., (Copyright © 2010 Elsevier Inc. All rights reserved.)
- Published
- 2010
- Full Text
- View/download PDF