The triiodothyronine nuclear receptor c-ErbA alpha 1 inhibits avian MyoD transcriptional activity in myoblasts

Thyroid hormone stimulates myoblast differentiation, through an inhibition of AP-1 activity occurring at the onset of differentiation. In this study w e found that the T3 nuclear receptor c-ErbA alpha1 (T3R alpha1) is involved in a mechanism preserving the duration of myoblast proliferation. Independ ently of the hormone presence, T3R alpha1 represses avian MyoD transcriptio nal activity. Using several mutants of T3R alpha1, we found that the hinge region plays a crucial role in the inhibition of MyoD activity. In particul ar, mutations of two small basic sequences included in alpha helices abroga te the T3R alpha1/MyoD functional interaction. Similarly, the T3 receptor a lso represses myogenin transcriptional activity. Therefore, despite stimula ting avian myoblast differentiation by a T3-dependent pathway not involving myogenic factors, T3R alpha1 contributes to maintain an optimal myoblast p roliferation period by inhibiting MyoD and myogenin activity. (C) 2001 Fede ration of European Biochemical Societies. Published by Elsevier Science B.V . All rights reserved.