GCLM (F7J2D) Rabbit mAb #33381

Glutamate-cysteine ligase modifier subunit (GCLM) is a component of the heterodimeric enzyme glutamate-cysteine ligase (GCL), which catalyzes the rate-limiting step in glutathione (GSH) biosynthesis, a ubiquitous intracellular peptide that plays vital roles in antioxidant defense, detoxification, cell proliferation, and other cellular functions (1,2). GCLM is one of a set of inhibitory ferroptosis genes that are normally repressed by the transcription factor BACH1 (a regulator in heme and iron metabolism) but are coordinately upregulated upon induction of ferroptosis with erastin (3). Additionally, when cells are starved for cysteine, the non-canonical activity of GCL can catalyze the synthesis of γ-glutamyl-peptide, therefore maintaining glutamate homeostasis to protect cells against ferroptosis (4).

GCLM overexpression in bladder cancer is correlated with immune filtration and poor prognosis, and knockdown of GCLM can significantly suppress the colony formation ability of tumor cells, thus suggesting that GCLM is a potential therapeutic target (5). Indeed, in vitro treatment of BLCA cells with MTX-211, an EFGR and PI3K kinase inhibitor, promoted NFR2 degradation and subsequent downregulation of GCLM expression, resulting in decreased GSH levels and cell proliferation inhibition (6). Polymorphisms in the 5′ promoter region of GCLM are also associated with an increased risk of myocardial infarction (7), and GCLM may be implicated in other diseases where oxidative stress plays a significant role.