期刊
FEBS LETTERS
卷 584, 期 15, 页码 3323-3330出版社
WILEY
DOI: 10.1016/j.febslet.2010.07.013
关键词
Mcl-1; Mitochondrial matrix; Apoptosis
资金
- Academia Sinica [AS23-57]
- National Science Council of Taiwan [NSC 94-2320-B-001-017, 95-2320-B-001-006]
The full-length pro-survival protein Mcl-1 predominantly resides on the outer membrane of mitochondria. Here, we identified a mitochondrial matrix-localized isoform of Mcl-1 that lacks 33 amino acid residues at the N-terminus which serve both as a mitochondrial targeting and processing signal. Ectopically-expressed Mcl-1 without the N-terminal 33 residues failed to enter the mitochondrial matrix but retained wt-like activities both for interaction with BH3-only proteins and antiapoptosis. In contrast, the mitochondria, matrix-localized isoform failed to interact with BH3-only proteins and manifested an attenuated anti-apoptotic activity. This study reveals that import of Mcl-1 into the mitochondrial matrix results in the attenuation of Mcl-1's anti-apoptotic function. Structured summary: MINT-7965637: NOXA (uniprotkb:Q9JM54) physically interacts (MI:0915) with Mcl-1 (uniprotkb:P97287) by anti tag coimmunoprecipitation (MI:0007) MINT-7965699: Mcl-1 (uniprotkb:P97287) physically interacts (MI:0915) with Bim (uniprotkb:043521) by anti bait coimmunoprecipitation (MI:0006) MINT-7965655: Mcl-1 (uniprotkb:P97287) physically interacts (MI:0915) with NOXA (uniprotkb:Q9JM54) by anti bait coimmunoprecipitation (MI:0006) MINT-7965711: Bim (uniprotkb:043521) physically interacts (MI:0915) with Mcl-1 (uniprotkb:P97287) by anti tag coimmunoprecipitation (MI:0007) MINT-7965673: PUMA (uniprotkb:Q9BXH1) physically interacts (MI:0915) with Mcl-1 (uniprotkb:P97287) by anti tag coimmunoprecipitation (MI:0007) MINT-7965685: Mcl-1 (uniprotkb:P97287) physically interacts (MI:0915) with PUMA (uniprotkb:Q9BXH1) by anti bait coimmunoprecipitation (MI:0006) (C) 2010 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
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