Document Detail

Jun blockade of erythropoiesis: role for repression of GATA-1 by HERP2.
MedLine Citation:
PMID:  15314183     Owner:  NLM     Status:  MEDLINE    
Although Jun upregulation and activation have been established as critical to oncogenesis, the relevant downstream pathways remain incompletely characterized. In this study, we found that c-Jun blocks erythroid differentiation in primary human hematopoietic progenitors and, correspondingly, that Jun factors block transcriptional activation by GATA-1, the central regulator of erythroid differentiation. Mutagenesis of c-Jun suggested that its repression of GATA-1 occurs through a transcriptional mechanism involving activation of downstream genes. We identified the hairy-enhancer-of-split-related factor HERP2 as a novel gene upregulated by c-Jun. HERP2 showed physical interaction with GATA-1 and repressed GATA-1 transcriptional activation. Furthermore, transduction of HERP2 into primary human hematopoietic progenitors inhibited erythroid differentiation. These results thus define a novel regulatory pathway linking the transcription factors c-Jun, HERP2, and GATA-1. Furthermore, these results establish a connection between the Notch signaling pathway, of which the HERP factors are a critical component, and the GATA family, which participates in programming of cellular differentiation.
Kamaleldin E Elagib; Mang Xiao; Isa M Hussaini; Lorrie L Delehanty; Lisa A Palmer; Frederick K Racke; Michael J Birrer; Ganapath Shanmugasundaram; Michael A McDevitt; Adam N Goldfarb
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Molecular and cellular biology     Volume:  24     ISSN:  0270-7306     ISO Abbreviation:  Mol. Cell. Biol.     Publication Date:  2004 Sep 
Date Detail:
Created Date:  2004-08-17     Completed Date:  2004-09-30     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  8109087     Medline TA:  Mol Cell Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  7779-94     Citation Subset:  IM    
Copyright Information:
Copyright 2004 American Society for Microbiology
University of Virginia School of Medicine, P.O. Box 800904, Charlottesville, VA 22908, USA.
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MeSH Terms
Antigens, CD34
Basic Helix-Loop-Helix Transcription Factors
Cell Cycle Proteins / genetics,  metabolism*
Cell Differentiation
DNA-Binding Proteins / metabolism*
Erythroid-Specific DNA-Binding Factors
Erythropoiesis / physiology*
GATA1 Transcription Factor
Gene Expression Regulation*
Helix-Loop-Helix Motifs
Hematopoietic Stem Cells / cytology,  metabolism*
K562 Cells
Proto-Oncogene Proteins c-jun / genetics,  metabolism*
RNA, Small Interfering / genetics,  metabolism
Recombinant Fusion Proteins / genetics,  metabolism
Repressor Proteins / genetics,  metabolism*
Transcription Factors / metabolism*
Transcription, Genetic
Grant Support
Reg. No./Substance:
0/Antigens, CD34; 0/Basic Helix-Loop-Helix Transcription Factors; 0/Cell Cycle Proteins; 0/DNA-Binding Proteins; 0/Erythroid-Specific DNA-Binding Factors; 0/GATA1 Transcription Factor; 0/GATA1 protein, human; 0/HEY1 protein, human; 0/Hairy, HRT1 protein; 0/Proto-Oncogene Proteins c-jun; 0/RNA, Small Interfering; 0/Recombinant Fusion Proteins; 0/Repressor Proteins; 0/Transcription Factors

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