Document Detail

Disabled-2 is transcriptionally regulated by ICSBP and augments macrophage spreading and adhesion.
MedLine Citation:
PMID:  11823414     Owner:  NLM     Status:  MEDLINE    
Mice lacking transcription factor interferon consensus sequence binding protein (ICSBP) develop a syndrome similar to human chronic myeloid leukemia and are immunodeficient. In order to define the molecular mechanisms responsible for the cellular defects of ICSBP(-/-) mice, we used bone marrow-derived macrophages (BMM) to identify genes deregulated in the absence of ICSBP. Here, we report that disabled-2 (Dab2), a signal phosphoprotein, is transcriptionally up-regulated and accumulates in the cytoskeleton/membrane fraction of ICSBP(-/-) BMM. Moreover, our results revealed Dab2 as a novel IFN-gamma-response gene. Both ICSBP and the Ets-transcription factor PU.1 bind to the Dab2 promoter, whereby ICSBP represses PU.1-induced Dab2 promoter transactivation in vitro. Notably, repression of Dab2 expression by ICSBP is also found in myeloid progenitors. Overexpression of Dab2 leads to accelerated cell adhesion and spreading, accompanied by enhanced actin fiber formation. Furthermore, cell adhesion induces transient Dab2 phosphorylation and its translocation to the cytoskeletal/membrane fraction. Our results identify a novel role of Dab2 as an inducer of cell adhesion and spreading, and strongly suggest that the up-regulation of Dab2 contributes to the hematopoietic defect seen in ICSBP(-/-) mice.
Frank Rosenbauer; Axel Kallies; Marina Scheller; Klaus-Peter Knobeloch; Charles O Rock; Maike Schwieger; Carol Stocking; Ivan Horak
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The EMBO journal     Volume:  21     ISSN:  0261-4189     ISO Abbreviation:  EMBO J.     Publication Date:  2002 Feb 
Date Detail:
Created Date:  2002-02-01     Completed Date:  2002-03-12     Revised Date:  2013-04-18    
Medline Journal Info:
Nlm Unique ID:  8208664     Medline TA:  EMBO J     Country:  England    
Other Details:
Languages:  eng     Pagination:  211-20     Citation Subset:  IM    
Department of Molecular Genetics, Institute of Molecular Pharmacology, and Benjamin Franklin Medical Center, Free University of Berlin, Krahmerstrasse 6, D-12207 Berlin, Germany.
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MeSH Terms
Adaptor Proteins, Signal Transducing
Adaptor Proteins, Vesicular Transport*
Cell Adhesion / genetics
Genes, Tumor Suppressor
Hematopoiesis / genetics
Interferon Regulatory Factors
K562 Cells
Macrophages / cytology,  physiology*
Promoter Regions, Genetic / genetics
Proteins / genetics*
Proto-Oncogene Proteins / genetics
Repressor Proteins / genetics*
Trans-Activators / genetics
Transcriptional Activation*
Reg. No./Substance:
0/Adaptor Proteins, Signal Transducing; 0/Adaptor Proteins, Vesicular Transport; 0/DAB2 protein, human; 0/Interferon Regulatory Factors; 0/Proteins; 0/Proto-Oncogene Proteins; 0/Repressor Proteins; 0/Trans-Activators; 0/interferon regulatory factor-8; 0/proto-oncogene protein Spi-1

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