Differential effects of Mxi1-SRalpha and Mxi1-SRbeta in Myc antagonism.
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.
Dugast-Darzacq
Claire
C
Department of Molecular Genetics, Albert Einstein College of Medicine, Bronx, NY, USA. darzacq@ijm.jussieu.fr
Grange
Thierry
T
Schreiber-Agus
Nicole B
NB
D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D018076:DNA, Complementary; D004591:Electrophoresis, Polyacrylamide Gel; D019143:Evolution, Molecular; D005455:Fluorescent Antibody Technique; D006801:Humans; D013058:Mass Spectrometry; D009955:Ornithine Decarboxylase / Q000235:genetics; D010957:Plasmids; D011401:Promoter Regions, Genetic; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000502:physiology*
D051792:Basic Helix-Loop-Helix Proteins; D018076:DNA, Complementary; D009955:Ornithine Decarboxylase; D016271:Proto-Oncogene Proteins c-myc; D025521:Tumor Suppressor Proteins; C079440:MXI1 protein, human