Glutathione-specific gamma-glutamylcyclotransferase 1 (CHAC1)

Glutathione-specific gamma-glutamylcyclotransferase 1 (CHAC1) is a cytosolic enzyme that specifically degrades glutathione, producing 5-oxoproline and cysteinylglycine[2]. It is an essential regulator of oxidative stress, apoptosis, and ferroptosis, and is highly induced during endoplasmic reticulum stress and as part of the unfolded protein response (UPR)[1][2]. CHAC1 is regulated by transcription factors, notably ATF4 and ATF3, and also modulates Notch signaling by binding and limiting the processing of Notch receptors, impacting differentiation and tumorigenesis[1]. Aberrant expression and activity of CHAC1 play roles in cancer progression, neurodegeneration, cardiovascular diseases, and kidney disease, highlighting its relevance as both a biomarker and a potential therapeutic target[1][3]. Elevated levels are linked to increased sensitivity to cell death under oxidative stress; however, inhibition of CHAC1 may be protective in some diseases by preserving intracellular glutathione and preventing excessive cell loss[1][2][3].

Other names

ChaC glutathione specific gamma-glutamylcyclotransferase 1CHAC1BotchGamma-GCG 1Glutathione-specific gamma-glutamylcyclotransferase 1Blocks Notch proteinCation transport regulator-like protein 1Gamma-GCT acting on glutathione homolog 1Cation transport regulator homolog 1MGC4504

Drugs or approaches targeting CHAC1 modulate intracellular glutathione levels, thereby affecting cellular redox status and cell death sensitivity (e.g., increased ferroptosis)[1]. Inhibition or upregulation of CHAC1 alters sensitivity to oxidative stress and cell fate by promoting or blocking glutathione degradation[1].