INCREASE IN P202 EXPRESSION DURING SKELETAL-MUSCLE DIFFERENTIATION - INHIBITION OF MYOD PROTEIN EXPRESSION AND ACTIVITY BY P202

p202 is a primarily nuclear, interferon-inducible murine protein that is encoded by the Ifi 202 gene. Overexpression of p202 in transfected cells retards cell proliferation. p202 modulates the pattern of gene e xpression by inhibiting the activity of various transcription factors including NF-kappa B, c-Fos, c-Jun, E2F-1, and p53. Were we report tha t p202 was constitutively expressed in mouse skeletal muscle and that the levels of 202 RNA and p202 greatly increased during the differenti ation of cultured C2C12 myoblasts to myotubes, When overexpressed in t ransfected myoblasts, p202 inhibited the expression of one muscle prot ein (MyoD) without affecting the expression of a second one (myogenin) . Thus, the decrease in the level of MyoD (but not of myogenin) during muscle differentiation may be the consequence of the increase in p202 level. Overexpressed p202 also inhibited the transcriptional activity of both MyoD and myogenin. This inhibition was correlated with an int eraction of p202 with both proteins, as web as the inhibition by p202 of the sequence-specific binding of both proteins to DNA. This inhibit ion of the expression of MyoD and of the transcriptional activity of M yoD and myogenin may account for the inhibition of the induction of my oblast differentiation by premature overexpression of p202.