MYBBP1a is a novel repressor of NF-kappaB.
NF-kappaB is an inducible transcription factor activated in many different cell types by inflammatory and stress signals. The transcription of a wide variety of NF-kappaB genes is regulated by the coordinated action of transcription co-activators and co-repressors. Previously we identified Myb binding protein 1a (MYBBP1a) as an interaction partner of the transcription activation domain of RelA/p65. MYBBP1a has been shown by others to regulate various transcription factors, through largely unknown mechanisms. Here we present evidence that MYBBP1a is a novel co-repressor of NF-kappaB. MYBBP1a interacted directly with RelA/p65 and expression of MYBBP1a in cells repressed NF-kappaB dependent reporter expression but did affect neither RelA/p65 nuclear translocation nor its DNA binding activity. In vitro, MYBBP1a inhibited transcription from chromatinized templates at a step before pre-initiation complex formation. MYBBP1a was found to compete with the histone acetyl transferase co-activator, p300, for interaction with the transcription activation domain of RelA/p65. Expression levels of MYBBP1a are dependent on the cell type, and are particularly high in Jurkat T cells. These results indicate that MYBBP1a is a novel NF-kappaB co-repressor of transcription that competes with p300 and may function to regulate cell type specific genes.
Owen
Heather R
HR
Institute of Veterinary Biochemistry and Molecular Biology, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland.
Elser
Michael
M
Cheung
Edwin
E
Gersbach
Monika
M
Kraus
W Lee
WL
Hottiger
Michael O
MO
D021581:Active Transport, Cell Nucleus; D001667:Binding, Competitive; D002466:Cell Nucleolus / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins; D017930:Genes, Reporter; D006367:HeLa Cells; D006801:Humans; D019169:Jurkat Cells; D009687:Nuclear Proteins / Q000378:metabolism*; D029543:Nucleocytoplasmic Transport Proteins / Q000378:metabolism*; D009707:Nucleosomes / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D016601:RNA-Binding Proteins; D012097:Repressor Proteins / Q000378:metabolism*; D051996:Transcription Factor RelA / Q000737:chemistry / Q000378:metabolism*; D014157:Transcription Factors; D014158:Transcription, Genetic; D015533:Transcriptional Activation / Q000235:genetics; D050880:p300-CBP Transcription Factors / Q000378:metabolism
D004268:DNA-Binding Proteins; C491719:MYBBP1A protein, human; D009687:Nuclear Proteins; D029543:Nucleocytoplasmic Transport Proteins; D009707:Nucleosomes; D016601:RNA-Binding Proteins; D012097:Repressor Proteins; D051996:Transcription Factor RelA; D014157:Transcription Factors; D004247:DNA; D050880:p300-CBP Transcription Factors