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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
8
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pubmed:dateCreated |
1999-3-18
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pubmed:abstractText |
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.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Calcium-Calmodulin-Dependent...,
http://linkedlifedata.com/resource/pubmed/chemical/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/DNA Primers,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/JNK Mitogen-Activated Protein...,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-fos,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-jun,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Macrophage...,
http://linkedlifedata.com/resource/pubmed/chemical/Tetradecanoylphorbol Acetate,
http://linkedlifedata.com/resource/pubmed/chemical/Thymidine Kinase,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators,
http://linkedlifedata.com/resource/pubmed/chemical/proto-oncogene protein Spi-1
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
19
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pubmed:volume |
274
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
4939-46
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:9988737-Animals,
pubmed-meshheading:9988737-Base Sequence,
pubmed-meshheading:9988737-Binding Sites,
pubmed-meshheading:9988737-Calcium-Calmodulin-Dependent Protein Kinases,
pubmed-meshheading:9988737-Cell Differentiation,
pubmed-meshheading:9988737-Cell Line,
pubmed-meshheading:9988737-DNA,
pubmed-meshheading:9988737-DNA Primers,
pubmed-meshheading:9988737-DNA-Binding Proteins,
pubmed-meshheading:9988737-Haplorhini,
pubmed-meshheading:9988737-JNK Mitogen-Activated Protein Kinases,
pubmed-meshheading:9988737-Mice,
pubmed-meshheading:9988737-Mitogen-Activated Protein Kinases,
pubmed-meshheading:9988737-Monocytes,
pubmed-meshheading:9988737-Phosphorylation,
pubmed-meshheading:9988737-Promoter Regions, Genetic,
pubmed-meshheading:9988737-Proto-Oncogene Proteins,
pubmed-meshheading:9988737-Proto-Oncogene Proteins c-fos,
pubmed-meshheading:9988737-Proto-Oncogene Proteins c-jun,
pubmed-meshheading:9988737-Receptor, Macrophage Colony-Stimulating Factor,
pubmed-meshheading:9988737-Tetradecanoylphorbol Acetate,
pubmed-meshheading:9988737-Thymidine Kinase,
pubmed-meshheading:9988737-Trans-Activators,
pubmed-meshheading:9988737-Transcriptional Activation,
pubmed-meshheading:9988737-Tumor Cells, Cultured,
pubmed-meshheading:9988737-Up-Regulation
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pubmed:year |
1999
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pubmed:articleTitle |
c-Jun is a JNK-independent coactivator of the PU.1 transcription factor.
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pubmed:affiliation |
Division of Hematology/Oncology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02115, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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