Document Detail

FLASH acts as a co-activator of the transcription factor c-Myb and localizes to active RNA polymerase II foci.
MedLine Citation:
PMID:  18408764     Owner:  NLM     Status:  MEDLINE    
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.
A H Alm-Kristiansen; T Saether; V Matre; S Gilfillan; O Dahle; O S Gabrielsen
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-04-14
Journal Detail:
Title:  Oncogene     Volume:  27     ISSN:  1476-5594     ISO Abbreviation:  Oncogene     Publication Date:  2008 Aug 
Date Detail:
Created Date:  2008-08-07     Completed Date:  2008-09-16     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  8711562     Medline TA:  Oncogene     Country:  England    
Other Details:
Languages:  eng     Pagination:  4644-56     Citation Subset:  IM    
Department of Molecular Biosciences, University of Oslo, Oslo, Norway.
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MeSH Terms
Apoptosis Regulatory Proteins / chemistry,  metabolism*,  physiology*
COS Cells
Calcium-Binding Proteins / chemistry,  metabolism*,  physiology*
Cell Nucleus / metabolism
Cells, Cultured
Cercopithecus aethiops
K562 Cells
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
Reg. No./Substance:
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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