Differential effects of Mxi1-SRalpha and Mxi1-SRbeta in Myc antagonism.

Claire Dugast-Darzacq (1, 2) , Thierry Grange (1) , Nicole B. Schreiber-Agus (2)

1 IJM (UMR_7592) - Institut Jacques Monod
2 Department of Molecular Genetics

Mxi1 belongs to the Myc-Max-Mad transcription factor network. Two Mxi1 protein isoforms, Mxi1-SRalpha and Mxi1-SRbeta, have been described as sharing many biological properties. Here, we assign differential functions to these isoforms with respect to two distinct levels of Myc antagonism. Unlike Mxi1-SRbeta, Mxi1-SRalpha is not a potent suppressor of the cellular transformation activity of Myc. Furthermore, although Mxi1-SRbeta exhibits a repressive effect on the MYC promoter in transient expression assays, Mxi1-SRalpha activates this promoter. A specific domain of Mxi1-SRalpha contributes to these differences. Moreover, glyceraldehyde-3-phosphate dehydrogenase interacts with Mxi1-SRalpha and enhances its ability to activate the Myc promoter. Our findings suggest that Mxi1 gains functional complexity by encoding isoforms with shared and distinct activities.

Mots clés: Mxi1; Myc; isoforms; REF assay; transcription; GAPDH

Domaines: Biochimie, Biologie Moléculaire

Claire Dugast-Darzacq, Thierry Grange, Nicole B. Schreiber-Agus. Differential effects of Mxi1-SRalpha and Mxi1-SRbeta in Myc antagonism.. FEBS Journal, 2007, 274 (17), pp.4643-53. ⟨10.1111/j.1742-4658.2007.05992.x⟩. ⟨hal-00181105⟩