CRBN controls TE phenotype by altering the dynamic regulation of MYC. (A) Myc protein levels in activated Crbn+/+ and Crbn−/− T cells (denoted + and −) were determined by immunoblot analysis at the indicated intervals after stimulation with anti-CD3ε+anti-CD28. The expression shown is relative to levels of β-actin, and the data are representative of 4 independent experiments. Values indicate band density of the western blot. (B) Myc mRNA levels in Crbn+/+ and Crbn−/− CD8+ T cells after activation by anti-CD3ε+anti-CD28 for the times indicated. (C) Diagram of MYC:MAX pharmacological disruption and (D) the structures of 10074-G5, MYCMI-11, and MYCMI-6 MYC:MAX inhibitors used. (E-F) CD8+ T cells were stimulated with anti-CD3ε+anti-CD28 for 24 hours, with or without cotreatment with the indicated doses of 10074-G5 or with 30 μM MYCMI-11 or MYCI-6 MYC/MAX dimerization inhibitors. Levels of Odc1 (E), and the TE signature genes Tbx21, Eomes, Gzmb, and Ifng transcripts in Crbn+/+and Crbn−/− CD8+ T cells (F). All results are representative of at least 2 independent experiments. n.s., not significant; *P < .05; **P < .01; ***P < .001; ****P < .0001.