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Publication : Dissection of the role of p62/Sqstm1 in activation of Nrf2 during xenophagy.

First Author  Ishimura R Year  2014
Journal  FEBS Lett Volume  588
Issue  5 Pages  822-8
PubMed ID  24492006 Mgi Jnum  J:206722
Mgi Id  MGI:5551910 Doi  10.1016/j.febslet.2014.01.045
Citation  Ishimura R, et al. (2014) Dissection of the role of p62/Sqstm1 in activation of Nrf2 during xenophagy. FEBS Lett 588(5):822-8
abstractText  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.
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