Document Detail

c-Jun is a JNK-independent coactivator of the PU.1 transcription factor.
MedLine Citation:
PMID:  9988737     Owner:  NLM     Status:  MEDLINE    
The ETS domain transcription factor PU.1 is necessary for the development of monocytes and regulates, in particular, the expression of the monocyte-specific macrophage colony-stimulating factor (M-CSF) receptor, which is critical for monocytic cell survival, proliferation, and differentiation. The bZIP transcription factor c-Jun, which is part of the AP-1 transcription factor complex, is also important for monocytic differentiation, but the monocyte-specific M-CSF receptor promoter has no AP-1 consensus binding sites. We asked the question of whether c-Jun could promote the induction of the M-CSF receptor by collaborating with PU.1. We demonstrate that c-Jun enhances the ability of PU.1 to transactivate the M-CSF receptor promoter as well as a minimal thymidine kinase promoter containing only PU.1 DNA binding sites. c-Jun does not directly bind to the M-CSF receptor promoter but associates via its basic domain with the ETS domain of PU.1. Consistent with our observation that AP-1 binding does not contribute to c-Jun coactivation is the observation that the activation of PU.1 by c-Jun is blocked by overexpression of c-Fos. Phosphorylation of c-Jun by c-Jun NH2-terminal kinase on Ser-63 and -73 does not alter the ability of c-Jun to enhance PU.1 transactivation. Activated Ras enhances the transcriptional activity of PU.1 by up-regulating c-Jun expression without changing the phosphorylation pattern of PU.1. The activation of PU.1 by Ras is blocked by a mutant c-Jun protein lacking the basic domain. The expression of this mutant form of c-Jun also completely blocks 12-O-tetradecanoylphorbol-13-acetate-induced M-CSF receptor promoter activity during monocytic differentiation. We propose therefore that c-Jun acts as a c-Jun NH2-terminal kinase-independent coactivator of PU.1, resulting in M-CSF receptor expression and development of the monocytic lineage.
G Behre; A J Whitmarsh; M P Coghlan; T Hoang; C L Carpenter; D E Zhang; R J Davis; D G Tenen
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  274     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  1999 Feb 
Date Detail:
Created Date:  1999-03-18     Completed Date:  1999-03-18     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  4939-46     Citation Subset:  IM    
Division of Hematology/Oncology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02115, USA.
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MeSH Terms
Base Sequence
Binding Sites
Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
Cell Differentiation
Cell Line
DNA / metabolism
DNA Primers
DNA-Binding Proteins / metabolism
JNK Mitogen-Activated Protein Kinases
Mitogen-Activated Protein Kinases*
Monocytes / cytology,  metabolism
Promoter Regions, Genetic
Proto-Oncogene Proteins / metabolism*
Proto-Oncogene Proteins c-fos / genetics
Proto-Oncogene Proteins c-jun / metabolism*
Receptor, Macrophage Colony-Stimulating Factor / genetics
Tetradecanoylphorbol Acetate / pharmacology
Thymidine Kinase / genetics
Trans-Activators / metabolism*
Transcriptional Activation
Tumor Cells, Cultured
Grant Support
Reg. No./Substance:
0/DNA Primers; 0/DNA-Binding Proteins; 0/Proto-Oncogene Proteins; 0/Proto-Oncogene Proteins c-fos; 0/Proto-Oncogene Proteins c-jun; 0/Trans-Activators; 0/proto-oncogene protein Spi-1; 16561-29-8/Tetradecanoylphorbol Acetate; 9007-49-2/DNA; EC Kinase; EC, Macrophage Colony-Stimulating Factor; EC Protein Kinases; EC Mitogen-Activated Protein Kinases; EC Protein Kinases

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