Extended Data Fig. 8: SCRN1 promotes the interaction of STK38 and GPX4.
a, GPX4 expression in WT and STK38 KO Huh7 cells with SCRN1 knockdown or not. b, The efficiency of stable SCRN1 overexpression in control and STK38 KO cells. c, STK38 expression in WT and SCRN1 KO HepG2 cells. d, e, The interaction between full length and truncations of STK38-Flag and SCRN1-Myc in HEK293T cells was detected by co-IP analysis. f, The interaction of STK38-Flag and SCRN1-Myc N truncations in HEK293T cells was detected by co-IP analysis. g, The phosphorylation of YAP1-V5 and interaction of STK38-Flag and YAP1-V5 in HEK293T cells was detected by co-IP analysis. h, i, The phosphorylation of YAP1 by STK38 in PDOs (h) (n = 4 PDOs) and HCC tumors (i) (n = 6 HCC tumors) was detected by in vitro kinase assays. j, The mRNA expression of c-MYC, PPAT, LDHA, BCAT1 and NPM1 in HepG2 and Huh7 cells with STK38 knockdown or not (PPAT: phosphoribosyl pyrophosphate amidotransferase, LDHA: lactate dehydrogenase A, BCAT1: branched chain amino acid transaminase 1, NPM1: nucleophosmin 1) (n = 3 biological replicates). k, l, The protein level of c-MYC in WT and STK38 KO HepG2 (k) and Huh7 (l) cells. m, The luciferase activity of c-MYC in HepG2 and Huh7 cells transfected with STK38 or control plasmid (n = 3 biological replicates). n, The mechanism of SCRN1 promoting ferroptosis resistance through enhancing GPX4 phosphorylation and abolishing CMA degradation of it via STK38 (created by Biorender). Data shown are representative of three independent experiments with similar results (a-i, k, l). Data presented as mean ± s.d. of three independent experiments (j, m) or mean ± s.e.m. (h, i). Statistical significance was determined by two-tailed unpaired Student’s t-test (j, m) or two-tailed paired Student’s t-test (h, i).