Document Detail

Human T-cell lymphotropic virus type 1 Tax represses c-Myb-dependent transcription through activation of the NF-kappaB pathway and modulation of coactivator usage.
MedLine Citation:
PMID:  11585920     Owner:  NLM     Status:  MEDLINE    
The proto-oncogene c-myb is essential for a controlled balance between cell growth and differentiation. Aberrant c-Myb activity has been reported for numerous human cancers, and enforced c-Myb transcription can transform cells of lymphoid origin by stimulating cellular proliferation and inhibiting apoptotic pathways. Here we demonstrate that activation of the NF-kappaB pathway by the HTLV-1 Tax protein leads to transcriptional inactivation of c-Myb. This conclusion was supported by the fact that Tax mutants unable to stimulate the NF-kappaB pathway could not inhibit c-Myb transactivating functions. In addition, inhibition of Tax-mediated NF-kappaB activation by coexpression of IkappaBalpha restored c-Myb transcription, and Tax was unable to block c-Myb transcription in a NEMO knockout cell line. Importantly, physiological stimuli, such as signaling with the cellular cytokines tumor necrosis factor alpha, interleukin 1 beta (IL-1beta), and lipopolysaccharide, also inhibited c-Myb transcription. These results uncover a new link between extracellular signaling and c-Myb-dependent transcription. The mechanism underlying NF-kappaB-mediated repression was identified as sequestration of the coactivators CBP/p300 by RelA. Interestingly, an amino-terminal deletion form of p300 lacking the C/H1 and KIX domains and unable to bind RelA retained the ability to stimulate c-Myb transcription and prevented NF-kappaB-mediated repression.
C Nicot; R Mahieux; C Pise-Masison; J Brady; A Gessain; S Yamaoka; G Franchini
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Molecular and cellular biology     Volume:  21     ISSN:  0270-7306     ISO Abbreviation:  Mol. Cell. Biol.     Publication Date:  2001 Nov 
Date Detail:
Created Date:  2001-10-04     Completed Date:  2001-12-04     Revised Date:  2013-04-17    
Medline Journal Info:
Nlm Unique ID:  8109087     Medline TA:  Mol Cell Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  7391-402     Citation Subset:  IM    
Section of Animal Models and Retroviral Vaccines, Basic Research Laboratory, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20892, USA.
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MeSH Terms
Cell Differentiation
Cell Division
Cell Line
DNA-Binding Proteins / metabolism
E1A-Associated p300 Protein
Enzyme Activation
Gene Deletion
Gene Products, tax / metabolism*
I-kappa B Proteins*
Interleukin-1 / metabolism
Ligases / metabolism
Luciferases / metabolism
Mice, Knockout
Microscopy, Fluorescence
NF-kappa B / metabolism*
Nuclear Proteins / metabolism
Plasmids / metabolism
Precipitin Tests
Protein Binding
Protein Structure, Tertiary
Proto-Oncogene Proteins c-myb / metabolism*
Reticulocytes / metabolism
Signal Transduction
Trans-Activators / metabolism
Transcription, Genetic*
Transcriptional Activation
Reg. No./Substance:
0/DNA-Binding Proteins; 0/Ep300 protein, mouse; 0/Gene Products, tax; 0/I-kappa B Proteins; 0/Interleukin-1; 0/NF-kappa B; 0/Nuclear Proteins; 0/Proto-Oncogene Proteins c-myb; 0/Trans-Activators; 139874-52-5/NF-kappaB inhibitor alpha; EC 1.13.12.-/Luciferases; EC p300 Protein; EC 6.-/Ligases; EC 6.-/guanosine 3',5'-polyphosphate synthetases

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