Seigo Terawaki    Department   Kawasaki Medical School  Kawasaki Medical School, Department of Molecular and Genetic Medicine,    Position   Assistant Professor with Special Assignment
Article types	原著
Language	English
Peer review	Peer reviewed
Title	Autophagy inhibition promotes defective neosynthesized proteins storage in ALIS, and induces redirection toward proteasome processing and MHCI-restricted presentation.
Journal	Formal name：Autophagy Abbreviation：Autophagy ISSN code：15548635/15548627
Domestic / Foregin	Foregin
Volume, Issue, Page	8(3),pp.350-363
Author and coauthor	Wenger Till, Terawaki Seigo, Camosseto Voahirana, Abdelrassoul Ronza, Mies Anna, Catalan Nadia, Claudio Nuno, Clavarino Giovanna, de Gassart Aude, Rigotti Francesca de Angelis, Gatti Evelina, Pierre Philippe
Authorship	Lead author
Publication date	2012/03
Summary	A significant portion of newly synthesized protein fails to fold properly and is quickly degraded. These defective ribosomal products (DRiPs) are substrates for the ubiquitin-proteasome system (UPS) and give rise to a large fraction of peptides presented by major histocompatibility complex class I molecules (MHCI). Here, we showed that DRiPs are also autophagy substrates, which accumulate upon autophagy inhibition in aggresome-like-induced structures (ALIS). Aggregation is critically depending on p62/SQSTM1, but occurs in the absence of activation of the NRF2 signaling axis and transcriptional regulation of p62/SQSTM1. We demonstrated that autophagy-targeted DRiPs can become UPS substrates and give rise to MHCI presented peptides upon autophagy inhibition. We further demonstrated that autophagy targeting of DRiPs is controlled by NBR1, but not p62/SQSTM1, CHIP or BAG-1. Active autophagy therefore directly modulates MHCI presentation by constantly degrading endogenous defective neosynthesized antigens, which are submitted to at least two distinct quality control mechanisms.
DOI	10.4161/auto.18806
PMID	22377621