Coactivation of nuclear receptors and myogenic factors induces the major BTG1 influence on muscle differentiation.
The btg1 (B-cell translocation gene 1) gene coding sequence was isolated from a translocation break point in a case of B-cell chronic lymphocytic leukaemia. We have already shown that BTG1, considered as an antiproliferative protein, strongly stimulates myoblast differentiation. However, the mechanisms involved in this influence remained unknown. In cultured myoblasts, we found that BTG1 stimulates the transcriptional activity of nuclear receptors (T3 and all-trans retinoic acid receptors but not RXRalpha and PPARgamma), c-Jun and myogenic factors (CMD1, Myf5, myogenin). Immunoprecipitation experiments performed in cells or using in vitro-synthesized proteins and GST pull-down assays established that BTG1 directly interacts with T3 and all-trans retinoic acid receptors and with avian MyoD (CMD1). These interactions are mediated by the transactivation domain of each transcription factor and the A box and C-terminal part of BTG1. NCoR presence induces the ligand dependency of the interaction with nuclear receptors. Lastly, deletion of BTG1 interacting domains abrogates its ability to stimulate nuclear receptors and CMD1 activity, and its myogenic influence. In conclusion, BTG1 is a novel important coactivator involved in the regulation of myoblast differentiation. It not only stimulates the activity of myogenic factors, but also of nuclear receptors already known as positive myogenic regulators.
Busson
Muriel
M
UMR 866 Différenciation Cellulaire et Croissance, INRA, 2 place Viala, 34060 Montpellier Cedex 1, France.
Carazo
Angel
A
Seyer
Pascal
P
Grandemange
Stéphanie
S
Casas
François
F
Pessemesse
Laurence
L
Rouault
Jean-Pierre
JP
Wrutniak-Cabello
Chantal
C
Cabello
Gérard
G
D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D032446:Myoblasts / Q000166:cytology*; D009363:Neoplasm Proteins / Q000737:chemistry / Q000502:physiology*; D011484:Protein-Arginine N-Methyltransferases / Q000502:physiology; D016755:Proto-Oncogene Proteins c-jun / Q000502:physiology; D018160:Receptors, Cytoplasmic and Nuclear / Q000502:physiology*; D014158:Transcription, Genetic
D006877:Hydroxamic Acids; D009363:Neoplasm Proteins; D016755:Proto-Oncogene Proteins c-jun; D018160:Receptors, Cytoplasmic and Nuclear; C074086:BTG1 protein, human; C012589:trichostatin A; D011484:Protein-Arginine N-Methyltransferases