Extended Data Fig. 7: Effect of protein kinase inhibition or activation on digoxin-mediated REV-ERBα protein level decrease.

WES analysis of REV-ERBα protein levels in synchronized human AC16 cells (a) treated with vehicle, digoxin (0.5 µM) and/or SRC inhibitor (saracatinib, 10 µM), (b) treated with vehicle, digoxin (0.5 µM) and/or PI3K inhibitor (LY294002, 20 µM) (c) treated with vehicle, digoxin (0.5 µM) and/or PI3K/P70S6K inhibitor (dactolisib, 0.1 µM), (d) transfected with ERK1 expression vector, (e) treated with the GSK3β inhibitor lithium (20 mM) and/or digoxin, (f) transfected with scrambled siRNA (Scr siRNA) or CAMK4 siRNA and treated with vehicle or digoxin (0.5 µM), (g) transfected with scrambled siRNA (Scr siRNA) or ERK1&3 siRNA and treated with vehicle or digoxin (0.5 µM), (h) transfected with scrambled siRNA (Scr siRNA) or PKD1 siRNA and treated with vehicle or digoxin (0.5 µM), (i) transfected with scrambled siRNA (Scr siRNA) or PKG1 siRNA and treated with vehicle or digoxin (0.5 µM), (j) transfected with scrambled siRNA (Scr siRNA) or HOIL siRNA and treated with vehicle or digoxin (0.5 µM) and (k) transfected with an empty (pcDNA3) or OTULIN-expressing (pcDNA3-OTULIN) vector and treated with vehicle or digoxin (0.5 µM).