Fig. 4.

Dependency of Dabrafenib (Dbr) and MK1775 (MK) translation effects on GCN2 and eIF2α. (A) TREEspot visualization of likelihood score (LS) for targets modulated by Dabrafenib and MK1775, and not by AZ628 (SI Appendix, Fig. S5 for target modulation by individual compounds, SI Appendix, Table S5 for LS values, and SI Appendix, Materials and Methods for LS definition). (B–G) Changes in RP translation under acute drug treatment (1 μM, 1 h) in HMEC-CT2 subjected to negative control siRNA, or siRNA targeting GCN2 (B–D) or eIF2α (E–G) (SI Appendix, Fig. S6 A–H for supporting data). Translation changes, measured by TPRT, are relative to normalization factor of non-RP internal controls, and DMSO vehicle control, as described in SI Appendix, Materials and Methods. Fold changes are derived as a mean of four (B–D) or three (E–G) biological replicates, each with three technical replicates; error bars denote SEs.