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Dissection of the role of p62/Sqstm1 in activation of Nrf2 during xenophagy
Author(s) -
Ishimura Ryosuke,
Tanaka Keiji,
Komatsu Masaaki
Publication year - 2014
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.2014.01.045
Subject(s) - chemistry , dissection (medical) , microbiology and biotechnology , biophysics , anatomy , biology
Upon infection of a cell by Salmonella , p62/Sqstm1 assembles on the microbes; simultaneously, p62/Sqstm1 is phosphorylated at Ser351, leading to inactivation of Keap1, which is responsible for degrading Nrf2. Thus, cytoprotective Nrf2 targets are induced at the same time that autophagosomes entrap the microbes (xenophagy). However, the detailed role of p62/Sqstm1 during xenophagy has remained unclear. Here we show that translocation of p62/Sqstm1 to invasive Salmonella precedes Ser351 phosphorylation. Furthermore, in addition to Ser351 phosphorylation, oligomerization of p62/Sqstm1 is also required for localization of Keap1 onto microbes, which is followed by Nrf2 activation. Our data reveal the sequential dynamics of p62/Sqstm1 in response to bacterial infection.