ATF4 deficiency increased phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) at threonine 202 and tyrosine 204, Jun N-terminal kinase (JNK) at threonine 183 and tyrosine 185, and eIF2α at serine 51, as well as p62 expression (Fig. 5G), which supports HCC development in MUP-uPA mice.5 Expression and phosphorylation of signal transducer and activator of transcription 3 (STAT3), AKT, and JNK, but not of ERK, were also increased in MUP-uPA/Atf4Δhep tumours isolated from 10-mo mice (Fig. S5F). This evidence concerns the gene PLAU and hepatocellular carcinoma.