| FLASH acts as a co-activator of the transcription factor c-Myb and localizes to active RNA polymerase II foci. | |
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MedLine Citation:
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PMID: 18408764 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The c-Myb oncoprotein is a DNA-binding transcription factor with a key role in early stages of hematopoiesis. To expand our knowledge of partners cooperating with c-Myb, we performed a yeast two-hybrid screening with full-length c-Myb as bait. Here, we report FLICE-associated huge protein (FLASH)/CASP8AP2 as a novel Myb-interacting protein. We show that FLASH interacts with the DNA-binding domain of c-Myb and enhances c-Myb-dependent reporter activity and expression of endogenous c-Myb target genes. Chromatin immunoprecipitation assays revealed that FLASH and c-Myb both associate with the MYC promoter region as well as with the intronic enhancer of the c-Myb target gene ADA. Furthermore, siRNA knock-down of FLASH or c-Myb both result in a reduction of MYC and ADA expression. The co-activator effect is mediated through the C-terminal part of FLASH, which binds c-Myb. The FLASH-induced enhancement is comparable with the increase seen with the c-Myb co-activator p300. We find FLASH localized in discrete nuclear speckles in several cell lines, co-localized with c-Myb in active RNA polymerase II foci. These results imply a novel molecular mechanism of regulation of c-Myb activity. We propose that c-Myb cooperates with FLASH in foci associated with active RNA polymerase II, leading to enhancement of Myb-dependent gene activation. |
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Authors:
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A H Alm-Kristiansen; T Saether; V Matre; S Gilfillan; O Dahle; O S Gabrielsen |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2008-04-14 |
Journal Detail:
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Title: Oncogene Volume: 27 ISSN: 1476-5594 ISO Abbreviation: Oncogene Publication Date: 2008 Aug |
Date Detail:
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Created Date: 2008-08-07 Completed Date: 2008-09-16 Revised Date: 2008-11-21 |
Medline Journal Info:
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Nlm Unique ID: 8711562 Medline TA: Oncogene Country: England |
Other Details:
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Languages: eng Pagination: 4644-56 Citation Subset: IM |
Affiliation:
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Department of Molecular Biosciences, University of Oslo, Oslo, Norway. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Apoptosis Regulatory Proteins / chemistry, metabolism*, physiology* COS Cells Calcium-Binding Proteins / chemistry, metabolism*, physiology* Cell Nucleus / metabolism Cells, Cultured Cercopithecus aethiops Humans K562 Cells Mice NIH 3T3 Cells Protein Binding Protein Structure, Tertiary / physiology Proto-Oncogene Proteins c-myb / chemistry, metabolism*, physiology RNA Polymerase II / metabolism* Tissue Distribution Trans-Activators / physiology Transcription Factors / physiology Transcriptional Activation / physiology |
| Chemical | |
Reg. No./Substance:
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0/Apoptosis Regulatory Proteins; 0/CASP8AP2 protein, human; 0/Calcium-Binding Proteins; 0/Proto-Oncogene Proteins c-myb; 0/Trans-Activators; 0/Transcription Factors; EC 2.7.7.-/RNA Polymerase II |
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