CBP and histone deacetylase inhibition enhance the transactivation potential of the HOXB7 homeodomain-containing protein.
Homeodomain-containing proteins are transcription factors regulating the coordinated expression of multiple target genes involved in development, differentiation and cellular transformation. In this study, we demonstrated that HOXB7, one member of this family, behaved as a transactivator in breast cancer cells. Deletion of either the HOXB7 N-terminal domain or the C-terminal acidic tail abolished this transcriptional effect, suggesting a combination of distinct functional transactivating domains. HOXB7 physically interacted both in vitro and in vivo with the coactivator CREB-binding protein (CBP). This interaction led to an enhanced transactivating potential and required the N-terminal of HOXB7 as well as two domains located at the C-terminal part of CBP. Moreover, trichostatin A, a deacetylase inhibitor, strongly enhanced the transcriptional properties of HOXB7. Our data therefore indicate that HOX proteins can directly interact with CBP and that acetylation/deacetylation may regulate their transcriptional properties.
Chariot
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A
Laboratory of Medical Chemistry and Medical Oncology, CHU B35, University of Liege Sart-Tilman, Belgium.
van Lint
C
C
Chapelier
M
M
Gielen
J
J
Merville
M P
MP
Bours
V
V
D001943:Breast Neoplasms; D050882:CREB-Binding Protein; D017362:Cyclic AMP Response Element-Binding Protein / Q000502:physiology*; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000235:genetics / Q000502:physiology*; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology*; D006801:Humans; D009687:Nuclear Proteins / Q000502:physiology*; D010446:Peptide Fragments / Q000235:genetics / Q000502:physiology; D010957:Plasmids / Q000138:chemical synthesis; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology*; D015533:Transcriptional Activation / Q000502:physiology*; D014162:Transfection; D014407:Tumor Cells, Cultured
D017362:Cyclic AMP Response Element-Binding Protein; D004791:Enzyme Inhibitors; C490538:HOXB7 protein, human; D056572:Histone Deacetylase Inhibitors; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; D010446:Peptide Fragments; D015534:Trans-Activators; D050882:CREB-Binding Protein; C494363:CREBBP protein, human; D006655:Histone Deacetylases