論文 - 詳細
| RRC ID | 59769 |
|---|---|
| 著者 | Ko PJ, Woodrow C, Dubreuil MM, Martin BR, Skouta R, Bassik MC, Dixon SJ. |
| タイトル | A ZDHHC5-GOLGA7 Protein Acyltransferase Complex Promotes Nonapoptotic Cell Death. |
| ジャーナル | Cell Chem Biol |
| Abstract |
Lethal small molecules are useful probes to discover and characterize novel cell death pathways and biochemical mechanisms. Here we report that the synthetic oxime-containing small molecule caspase-independent lethal 56 (CIL56) induces an unconventional form of nonapoptotic cell death distinct from necroptosis, ferroptosis, and other pathways. CIL56-induced cell death requires a catalytically active protein S-acyltransferase complex comprising the enzyme ZDHHC5 and an accessory subunit GOLGA7. The ZDHHC5-GOLGA7 complex is mutually stabilizing and localizes to the plasma membrane. CIL56 inhibits anterograde protein transport from the Golgi apparatus, which may be lethal in the context of ongoing ZDHHC5-GOLGA7 complex-dependent retrograde protein trafficking from the plasma membrane to internal sites. Other oxime-containing small molecules, structurally distinct from CIL56, may trigger cell death through the same pathway. These results define an unconventional form of nonapoptotic cell death regulated by protein S-acylation. |
| 巻・号 | 26(12) |
| ページ | 1716-1724.e9 |
| 公開日 | 2019-12-19 |
| DOI | 10.1016/j.chembiol.2019.09.014 |
| PII | S2451-9456(19)30319-8 |
| PMID | 31631010 |
| MeSH | Acylation Acyltransferases / chemistry Acyltransferases / genetics Acyltransferases / metabolism* Animals Cell Death* / drug effects Cell Line Cell Membrane / metabolism Fused-Ring Compounds / chemistry Fused-Ring Compounds / pharmacology Golgi Apparatus / drug effects Golgi Apparatus / metabolism Golgi Apparatus / ultrastructure Golgi Matrix Proteins / chemistry Golgi Matrix Proteins / genetics Golgi Matrix Proteins / metabolism* Humans Mice Oximes / chemistry Oximes / pharmacology Protein S / metabolism Protein Transport / drug effects |
| IF | 6.762 |
| 引用数 | 2 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 18 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.2 |
| リソース情報 | |
| ヒト・動物細胞 | Atg5^(+/+)MEF(RCB2710) Atg5^(-/-)MEF(RCB2711) |