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Ubiquitylation-independent ER-associated degradation of an AE1 mutant associated with dominant hereditary spherocytosis in cattle

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タイトル: Ubiquitylation-independent ER-associated degradation of an AE1 mutant associated with dominant hereditary spherocytosis in cattle
著者: Ito, Daisuke 著作を一覧する
Koshino, Ichiro 著作を一覧する
Arashiki, Nobuto 著作を一覧する
Adachi, Hirokazu 著作を一覧する
Tomihari, Mizuki 著作を一覧する
Tamahara, Satoshi 著作を一覧する
Kurogi, Kazuhito 著作を一覧する
Amano, Takashi 著作を一覧する
Ono, Ken-ichiro 著作を一覧する
Inaba, Mutsumi 著作を一覧する
キーワード: ER-associated degradation (ERAD)
Dominant negative
Hereditary spherocytosis
発行日: 2006年 9月 1日
出版者: The Company of Biologists Ltd
誌名: Journal of Cell Science
巻: 119
号: 17
開始ページ: 3602
終了ページ: 3612
出版社 DOI: 10.1242/jcs.03101
抄録: Various mutations in the AE1 (anion exchanger 1, band 3) gene cause dominant hereditary spherocytosis, a common congenital hemolytic anemia associated with deficiencies of AE1 of different degrees and loss of mutant protein from red blood cell membranes. To determine the mechanisms underlying decreases in AE1 protein levels, we employed K562 and HEK293 cell lines and Xenopus oocytes together with bovine wild-type AE1 and an R664X nonsense mutant responsible for dominant hereditary spherocytosis to analyze protein expression, turnover, and intracellular localization. R664X-mutant protein underwent rapid degradation and caused specifically increased turnover and impaired trafficking to the plasma membrane of the wild-type protein through hetero-oligomer formation in K562 cells. Consistent with those observations, co-expression of mutant and wild-type AE1 reduced anion transport by the wild-type protein in oocytes. Transfection studies in K562 and HEK293 cells revealed that the major pathway mediating degradation of both R664X and wild-type AE1 employed endoplasmic reticulum (ER)-associated degradation through the proteasomal pathway. Proteasomal degradation of R664X protein appeared to be independent of both ubiquitylation and N-glycosylation, and aggresome formation was not observed following proteasome inhibition. These findings indicate that AE1 R664X protein, which is associated with dominant hereditary spherocytosis, has a dominant-negative effect on the expression of wild-type AE1.
Rights: Reproduced with permission of the Company of Biologists.
資料タイプ: article (author version)
出現コレクション:雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

提供者: 稲葉 睦


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