Chemoproteomic Profiling of Erastin-Interacting Proteins.
Chem Res Toxicol
; 37(1): 109-116, 2024 01 15.
Article
em En
| MEDLINE
| ID: mdl-38173279
ABSTRACT
Ferroptosis is an iron-related cell death caused by irregular lipid peroxidation that has been implicated with a variety of disease. Erastin is a canonical ferroptosis inducer that is known to function by inhibiting system Xc- and cystine transport; however, the global interactome of erastin in cells remains unexplored. In this work, we employed a quantitative chemoproteomic approach to profile direct interacting proteins of erastin in living cells using a multifunctional photo-cross-linking probe. A number of novel erastin-interacting proteins were identified, including a serine hydrolase, ABHD6, whose overexpression showed a potentiating impact on ferroptosis. Further biochemical experiments revealed that erastin can allosterically activate ABHD6's activity to produce more arachidonic acids and elevate the level of lipid reactive oxygen species. Collectively, our work provided a global portrait of erastin-interacting proteins and discovered ABHD6 as a new ferroptosis regulator.
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Base de dados:
MEDLINE
Assunto principal:
Piperazinas
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article