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Identification of essential sequences for cellular localization in the muscle‐specific ubiquitin E3 ligase MAFbx/Atrogin 1
Author(s) -
Julie Lagirand-Cantaloube,
Sabrina Batonnet-Pichon,
Marie-Pierre Leibovitch,
Leibovitch Serge A.
Publication year - 2012
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2011.12.031
Subject(s) - ubiquitin ligase , nls , muscle atrophy , downregulation and upregulation , ubiquitin , microbiology and biotechnology , nuclear localization sequence , cytoplasm , chemistry , cytosol , dna ligase , skeletal muscle , biophysics , biochemistry , biology , anatomy , dna , gene , enzyme
In skeletal muscle atrophy, upregulation and nuclear accumulation of the Ubiquitin E3 ligase MAFbx is essential for accelerated muscle protein loss, but the nuclear/cytoplasmic shuttling of MAFbx is undefined. Here we found that MAFbx contains two functional nuclear localization signals (NLS). Mutation or deletion of only one NLS induced cytoplasmic localization of MAFbx. We identified a non‐classical NES located in the leucine charged domain (LCD) of MAFbx, which is leptomycin B insensitive. We demonstrated that mutation (L169Q) in LLXXL motif of LCD suppressed cytoplasmic retention of MAFbx. Nucleocytoplasmic shuttling of MAFbx represents a novel mechanism for targeting its substrates and its cytosolic partners in muscle atrophy.