Transcriptional repression by Pax5 (BSAP) through interaction with corepressors of the Groucho family.
Pax5 (BSAP) functions as both a transcriptional activator and repressor during midbrain patterning, B-cell development and lymphomagenesis. Here we demonstrate that Pax5 exerts its repression function by recruiting members of the Groucho corepressor family. In a yeast two-hybrid screen, the groucho-related gene product Grg4 was identified as a Pax5 partner protein. Both proteins interact cooperatively via two separate domains: the N-terminal Q and central SP regions of Grg4, and the octapeptide motif and C-terminal transactivation domain of Pax5. The phosphorylation state of Grg4 is altered in vivo upon Pax5 binding. Moreover, Grg4 efficiently represses the transcriptional activity of Pax5 in an octapeptide-dependent manner. Similar protein interactions resulting in transcriptional repression were also observed between distantly related members of both the Pax2/5/8 and Groucho protein families. In agreement with this evolutionary conservation, the octapeptide motif of Pax proteins functions as a Groucho-dependent repression domain in Drosophila embryos. These data indicate that Pax proteins can be converted from transcriptional activators to repressors through interaction with corepressors of the Groucho protein family.
Eberhard
D
D
Research Institute of Molecular Pathology, Dr Bohr-Gasse 7, A-1030 Vienna, Austria and Departamento de Biologia Molecular i Cellular, CID-CSIC, Jordi Girona 18-26, 08034 Barcelona, Spain.
Jiménez
G
G
Heavey
B
B
Busslinger
M
M
D016475:3T3 Cells; D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D051757:PAX5 Transcription Factor; D011506:Proteins / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics*; D015534:Trans-Activators / Q000235:genetics; D014157:Transcription Factors; D014158:Transcription, Genetic; D015533:Transcriptional Activation
D004268:DNA-Binding Proteins; D051757:PAX5 Transcription Factor; C497282:Pax5 protein, mouse; D011506:Proteins; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors