フジタ　トシハル   Toshiharu Fujita   藤田　敏治    所属   川崎医科大学  医学部 基礎医学　分子遺伝医学    職種   助教
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Ubiquitination of exposed glycoproteins by SCFFBXO27 directs damaged lysosomes for autophagy.
掲載誌名	正式名：Proceedings of the National Academy of Sciences of the United States of America 略　 称：Proc Natl Acad Sci U S A ISSNコード：10916490/00278424
掲載区分	国外
巻・号・頁	114(32),pp.8574-8579
著者・共著者	Yukiko Yoshida, Sayaka Yasuda, Toshiharu Fujita, Maho Hamasaki, Arisa Murakami, Junko Kawawaki, Kazuhiro Iwai, Yasushi Saeki, Tamotsu Yoshimori, Noriyuki Matsuda, Keiji Tanaka
発行年月	2017/08
概要	Ubiquitination functions as a signal to recruit autophagic machinery to damaged organelles and induce their clearance. Here, we report the characterization of FBXO27, a glycoprotein-specific F-box protein that is part of the SCF (SKP1/CUL1/F-box protein) ubiquitin ligase complex, and demonstrate that SCFFBXO27 ubiquitinates glycoproteins in damaged lysosomes to regulate autophagic machinery recruitment. Unlike F-box proteins in other SCF complexes, FBXO27 is subject to N-myristoylation, which localizes it to membranes, allowing it to accumulate rapidly around damaged lysosomes. We also screened for proteins that are ubiquitinated upon lysosomal damage, and identified two SNARE proteins, VAMP3 and VAMP7, and five lysosomal proteins, LAMP1, LAMP2, GNS, PSAP, and TMEM192. Ubiquitination of all glycoproteins identified in this screen increased upon FBXO27 overexpression. We found that the lysosomal protein LAMP2, which is ubiquitinated preferentially on lysosomal damage, enhances autophagic machinery recruitment to damaged lysosomes. Thus, we propose that SCFFBXO27 ubiquitinates glycoproteins exposed upon lysosomal damage to induce lysophagy.
DOI	10.1073/pnas.1702615114
PMID	28743755