| 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
|
| リソース情報 |
| ヒト・動物細胞 |
Atg5^(+/+)MEF(RCB2710)
Atg5^(-/-)MEF(RCB2711) |
