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TAK 1 converts Sequestosome 1/p62 from an autophagy receptor to a signaling platform
Author(s) -
Kehl Stephanie R,
Soos BrandyLee A,
Saha Bhaskar,
Choi Seong Won,
Herren Anthony W,
Johansen Terje,
Mandell Michael A
Publication year - 2019
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201846238
Subject(s) - library science , sequestosome 1 , center of excellence , health science , gerontology , medicine , biology , political science , genetics , autophagy , medical education , computer science , apoptosis , law
The protein p62/Sequestosome 1 (p62) has been described as a selective autophagy receptor and independently as a platform for pro‐inflammatory and other intracellular signaling. How these seemingly disparate functional roles of p62 are coordinated has not been resolved. Here, we show that TAK 1, a kinase involved in immune signaling, negatively regulates p62 action in autophagy. TAK 1 reduces p62 localization to autophagosomes, dampening the autophagic degradation of both p62 and p62‐directed autophagy substrates. TAK 1 also relocalizes p62 into dynamic cytoplasmic bodies, a phenomenon that accompanies the stabilization of TAK 1 complex components. On the other hand, p62 facilitates the assembly and activation of TAK 1 complexes, suggesting a connection between p62's signaling functions and p62 body formation. Thus, TAK 1 governs p62 action, switching it from an autophagy receptor to a signaling platform. This ability of TAK 1 to disable p62 as an autophagy receptor may allow certain autophagic substrates to accumulate when needed for cellular functions.