The interferon- and differentiation-inducible p202a protein inhibits the transcriptional activity of c-Myc by blocking its association with Max

p202a is a murine protein that is induced during the fusion of myoblasts to myotubes and can also be induced by interferon. Even 23-fold overexpressio n of p202a in cells retards proliferation. p202a was shown to modulate tran scription by binding, and inhibiting the activity of several transcription factors including c-Fos, c-Jun, AP-2, E2F1, E2F4, NF-kappa B, MyoD, and myo genin, Here we report that p202a also bound the c-Myc protein in vitro and in vivo; the C-terminal p202a b segment bound the C-terminal basic region h elix-loop-helix-leucine zipper (bHLHLZ) region of c-Myc. The transfection o f a p202a expression plasmid inhibited the c-Myc-dependent expression of re porter plasmids in transient assays; moreover, overexpression of p202a in s table cell lines decreased the endogenous levels of mRNAs whose expression is driven by c-Myc, These effects of p202a are consistent with our finding that the binding of p202a to c-Myc inhibited the binding of c-Myc to Max in vitro and in vivo. p202a also inhibited the e-Myc-induced anchorage-indepe ndent growth and apoptosis of Rat-1 cells. The inhibition of c-Myc-dependen t transcription, proliferation, and apoptosis by p202a is in line with the involvement of p202a in differentiation.