Document Detail

Physical interaction between retinoic acid receptor and the oncoprotein myb inhibits retinoic acid-dependent transactivation.
MedLine Citation:
PMID:  9576918     Owner:  NLM     Status:  MEDLINE    
The c-myb protooncogene is predominantly expressed in hematopoietic cells and plays a vital role in hematopoiesis. Retinoic acid (RA) is able to induce differentiation of several hematopoietic cells. This differentiation is linked to decreased c-myb expression, suggesting that retinoid receptors (RAR/RXR) may down-regulate c-myb gene expression. Furthermore, recent data indicate that RAR inhibits the function of the Myb protein itself. In addition, the Myb-Ets oncogenic fusion protein has been shown to inhibit transcriptional activation by RAR and thyroid hormone receptor. Myb-Ets also antagonizes the biological response of erythrocytic progenitor cells to RA and thyroid hormone. This prompted us to investigate a possible cross talk between RAR and Myb. Here, we demonstrate that RA inhibits the expression of the endogenous Myb target gene tom-1. Conversely, Myb functions as a potent inhibitor of RA-induced biological responses. Functional analysis of Myb mutants in transfection studies revealed that the Myb DNA-binding domain (DBD) is necessary for repression whereas the transactivation domain is dispensable. Furthermore, we show that v-Myb and RAR interact in vitro and in vivo. This interaction requires the DBD of RAR. In contrast, glutathione S-transferase-pulldown assays with v-Myb mutants indicate that the DBD and the C terminus of Myb directly interact with RAR. Our results suggest that the physical interaction between Myb and RAR may play a role in the regulation of hematopoietic gene expression.
E Pfitzner; J Kirfel; P Becker; A Rolke; R Schüle
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  95     ISSN:  0027-8424     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  1998 May 
Date Detail:
Created Date:  1998-06-19     Completed Date:  1998-06-19     Revised Date:  2013-04-16    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  5539-44     Citation Subset:  IM    
Institut für Experimentelle Krebsforschung, Klinik für Tumorbiologie an der Universität Freiburg, Breisacherstrasse 117, 79106 Freiburg, Germany.
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MeSH Terms
3T3 Cells
Binding Sites
COS Cells
DNA / metabolism
DNA-Binding Proteins / metabolism
Gene Expression Regulation / drug effects
Oncogene Proteins v-myb
Protein Binding
Proto-Oncogene Proteins / metabolism*
Proto-Oncogene Proteins c-myb
Receptors, Retinoic Acid / metabolism*
Recombinant Fusion Proteins / metabolism
Retinoid X Receptors
Retroviridae Proteins, Oncogenic / metabolism
Trans-Activators / metabolism*
Transcription Factors / metabolism
Transcriptional Activation* / drug effects
Tretinoin / metabolism*
Reg. No./Substance:
0/DNA-Binding Proteins; 0/Oncogene Proteins v-myb; 0/Proto-Oncogene Proteins; 0/Proto-Oncogene Proteins c-myb; 0/Receptors, Retinoic Acid; 0/Recombinant Fusion Proteins; 0/Retinoid X Receptors; 0/Retroviridae Proteins, Oncogenic; 0/Trans-Activators; 0/Transcription Factors; 302-79-4/Tretinoin; 9007-49-2/DNA

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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