Figure 3.

Genetic factors regulate cancer cell sensitivity to ferroptosis-inducing agents. (A) Proteins that can regulate GSH synthesis, iron hemostasis, or lipid metabolism alter the sensitivity of cancer cells to ferroptosis induction. These proteins include transcription factors (e.g., p53, ATF3, ATF4, and Nrf 2) and epigenetic factors (e.g., BAP1 and OTUB1) that regulate GPX4 translation/stability or expression of SLC7A11 and iron-regulatory genes (e.g., FPN), and enzymes (e.g., ACSL4) that regulate the synthesis of phospholipids (B) Multiple transcription factors and epigenetic factors bind to the human SLC7A11 promoter and regulate SLC7A11 transcription. Note that the p53-binding element (p53-BS) appears to be dispensable for the regulation of the activity of the human SLC7A11 promoter. ARE, antioxidant response element; AARE, amino acid response element; H2ub, ubiquitinated histone H2.