ATF4 and thyroid gland carcinoma: Interestingly, in both thyroid carcinoma cell lines, the top predicted upstream regulator of this gene set is ATF4 (Activating Transcription Factor 4, Fig. 1i and Supplementary Fig. 1i), leading to the hypothesis that activation of this transcription factor, a known mediator of the transcriptional program elicited by the ISR43, could explain some of the differential effects observed upon dual inhibition of p53 repressors.