Kinome screen of ferroptosis reveals a novel role of ATM in regulating iron metabolism

摘要

Kinome screening identified 34 kinase essential for cystine-deprived death. a Scatter plot displayed the effects of siRNA-mediated silencing of individual kinase on the viability of MDA-MB-231 under cystine-deprived (Y-axis) and full media (X-axis) upon the siRNA-mediated silencing of individual kinase in MADA-MB-231 breast cancer cells. Y-axis and X-axis are the relative cell viabilities after knockdown each kinase normalized against nontargeting control siRNA in cystine deprived and normal medium, respectively. Each purple dot represents individual kinase-targeting pooled siRNA; each red dot represents significant “hits” from the screen based on the log-transformed normalized viability and calculated by ANOVA (threshold: p < 0.0001). b List of 34 “hit” essential kinases is shown with their normalized viability (against nontarget siRNA) in the control full media or cystine-deprived media (ANOVA p < 0.0001). The kinases were ranked by the normalized viability under cystine deprivation. c STRING analysis of all the hit kinases based on the protein–protein interaction networks, highlighting the essential role of ATM and ATR as highly connecting nodes among the kinases essential for the cystine-deprived death