Fig. 5: MDM4 inhibits GPX4 degradation by switching its polyubiquitination from K48 to K63.
From: MDM4 inhibits ferroptosis in p53 mutant colon cancer via regulating TRIM21/GPX4 expression

A, B Effect of MDM4 overexpression or knockdown on GPX4 mRNA levels in HT29 cells (n = 3). C Effect of MG132 and CQ treatments on changes in GPX4 protein expression following MDM4 knockdown in HT29 cells. D CHX treatment showed GPX4 degradation kinetics following MDM4 overexpression in HT29 cells (n = 3). E Changes of GPX4 ubiquitination level following MDM4 expression. F Ubiquitylation assay showed MDM4 had no significant effect on K6, K11, K27, K29, and K33 ubiquitination, and promoted GPX4 polyubiquitination shift from K48 to K63. G Ubiquitylation assay showed the effect of Flag-GPX4 mutants on the GPX4 ubiquitination change induced by MDM4. ns: På 0.05;*P < 0.05; **P < 0.01; ***P < 0.001. A T test, B One-way ANOVA and D T test were used for statistical analysis.