テラワキ　セイゴウ   Seigo Terawaki   寺脇　正剛    所属   川崎医科大学  医学部 基礎医学　分子遺伝医学    職種   特任講師
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Autophagy inhibition promotes defective neosynthesized proteins storage in ALIS, and induces redirection toward proteasome processing and MHCI-restricted presentation.
掲載誌名	正式名：Autophagy 略　 称：Autophagy ISSNコード：15548635/15548627
掲載区分	国外
巻・号・頁	8(3),pp.350-363
著者・共著者	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
担当区分	筆頭著者
発行年月	2012/03
概要	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