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A ZDHHC5-GOLGA7 Protein Acyltransferase Complex Promotes Nonapoptotic Cell Death.

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.

journal_name

Cell Chem Biol

journal_title

Cell chemical biology

authors

Ko PJ,Woodrow C,Dubreuil MM,Martin BR,Skouta R,Bassik MC,Dixon SJ

doi

10.1016/j.chembiol.2019.09.014

subject

Has Abstract

pub_date

2019-12-19 00:00:00

pages

1716-1724.e9

issue

12

eissn

2451-9456

issn

2451-9448

pii

S2451-9456(19)30319-8

journal_volume

26

pub_type

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