CBP sensitizes v-myb-transformed monoblasts to differentiation inducers.
CREB-binding protein (CBP) regulates gene expression by binding to certain components of basal transcription machinery and by histone acetylation. In addition, it integrates various cellular signaling pathways through binding to multiple transcription factors, including the Myb proteins. We report in this study that CBP can partially suppress function of the v-Myb oncoprotein in leukemic cells. Although originally described as an activator of v-Myb function, we show that CBP can also act as a v-Myb suppressor. Ectopic expression of murine CBP in v-Myb-transformed chicken monoblasts reduced transcriptional activation abilities of the v-Myb protein and increased sensitivity to differentiation inducers such as phorbol ester or trichostatin A. In addition, exogenous CBP affected morphology of differentiated cells derived from BM2 monoblasts. These results indicate that cellular context is an important factor determining whether CBP will activate or suppress the protein it targets.
Smardová
Jana
J
Department of Pathology and Anatomy, University Hospital, Jihlavská 20, 625 00 Brno, Czech Republic.
Nemajerová
Alice
A
Navrátilová
Jarmila
J
Jurdic
Pierre
P
Smarda
Jan
J
D000818:Animals; D009189:Avian Myeloblastosis Virus / Q000502:physiology; D050882:CREB-Binding Protein; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002461:Cell Line, Transformed; D002472:Cell Transformation, Viral / Q000502:physiology; D002645:Chickens; D006877:Hydroxamic Acids / Q000494:pharmacology; D051379:Mice; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D020626:Oncogene Proteins v-myb / Q000502:physiology*; D010587:Phagocytosis / Q000502:physiology; D010703:Phorbol Esters / Q000494:pharmacology; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology*
D006877:Hydroxamic Acids; D009687:Nuclear Proteins; D020626:Oncogene Proteins v-myb; D010703:Phorbol Esters; D015534:Trans-Activators; C012589:trichostatin A; D050882:CREB-Binding Protein; C494364:Crebbp protein, mouse