The Interferon- and Differentiation-inducible p202a Protein Inhibits the Transcriptional Activity of c-Myc by Blocking Its Association with Max

Abstract

p202a is a murine protein that is induced during the fusion of myoblasts to myotubes and can also be induced by interferon. Even 2–3-fold overexpression of p202a in cells retards proliferation. p202a was shown to modulate transcription by binding, and inhibiting the activity of several transcription factors including c-Fos, c-Jun, AP-2, E2F1, E2F4, NF-κB, MyoD, and myogenin. Here we report that p202a also bound the c-Myc protein <i>in vitro</i> and<i>in vivo</i>; the C-terminal p202a <i>b</i> segment bound the C-terminal basic region helix-loop-helix-leucine zipper (bHLHLZ) region of c-Myc. The transfection of a p202a expression plasmid inhibited the c-Myc-dependent expression of reporter plasmids in transient assays; moreover, overexpression of p202a in stable 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 <i>in vitro</i> and <i>in vivo</i>. p202a also inhibited the c-Myc-induced anchorage-independent growth and apoptosis of Rat-1 cells. The inhibition of c-Myc-dependent transcription, proliferation, and apoptosis by p202a is in line with the involvement of p202a in differentiation.