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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
35
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pubmed:dateCreated |
1993-10-8
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pubmed:abstractText |
The early growth response 1 (EGR-1) gene is induced by mitogens, differentiating stimuli, and certain genotoxic agents in diverse cell types. The present work has examined the effects of 1-(beta-D-arabinofuranosyl)cytosine (ara-C), an antileukemia agent that misincorporates into DNA, on EGR-1 expression. Treatment of HL-525 myeloid leukemia cells with ara-C was associated with transient increases in EGR-1 mRNA levels. Nuclear run-on assays showed that this effect is related at least in part to activation of EGR-1 gene transcription. Sequences responsive to ara-C-induced signals were determined by deletion analysis of the EGR-1 promoter. The results demonstrate that ara-C inducibility of the EGR-1 gene is conferred by a region containing six serum response or CC(A/T)6GG (CArG) motifs. Further analysis demonstrated that the first two distal or 5'-most CArG elements are functional in the ara-C response. An oligomer corresponding to the first CArG element also conferred ara-C inducibility of the minimal thymdine kinase gene promoter, while no inducibility was detectable using a similar oligomer containing a mutated CArG box. Other work has demonstrated that the nuclear serum response factor (SRF) interacts with the CArG box in the EGR-1 promoter and that the serine/threonine pp90rsk protein kinase phosphorylates SRF in vitro at sites phosphorylated in vivo. The present studies demonstrate that ara-C has little if any effect on cytosolic pp90rsk as determined by immunoblotting to assess electrophoretic mobility and by immune-complex kinase assays using S6 peptide as substrate.(ABSTRACT TRUNCATED AT 250 WORDS)
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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/Chloramphenicol O-Acetyltransferase,
http://linkedlifedata.com/resource/pubmed/chemical/Cytarabine,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/EGR1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Early Growth Response Protein 1,
http://linkedlifedata.com/resource/pubmed/chemical/Immediate-Early Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/RNA,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Ribosomal Protein S6,
http://linkedlifedata.com/resource/pubmed/chemical/Ribosomal Protein S6 Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Ribosomal Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Serum Response Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0006-2960
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
7
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pubmed:volume |
32
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
9137-42
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:7690249-Base Sequence,
pubmed-meshheading:7690249-Cell Nucleus,
pubmed-meshheading:7690249-Chloramphenicol O-Acetyltransferase,
pubmed-meshheading:7690249-Cytarabine,
pubmed-meshheading:7690249-DNA Mutational Analysis,
pubmed-meshheading:7690249-DNA-Binding Proteins,
pubmed-meshheading:7690249-Early Growth Response Protein 1,
pubmed-meshheading:7690249-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:7690249-Humans,
pubmed-meshheading:7690249-Immediate-Early Proteins,
pubmed-meshheading:7690249-Leukemia, Myeloid,
pubmed-meshheading:7690249-Molecular Sequence Data,
pubmed-meshheading:7690249-Nuclear Proteins,
pubmed-meshheading:7690249-Protein-Serine-Threonine Kinases,
pubmed-meshheading:7690249-RNA,
pubmed-meshheading:7690249-RNA, Messenger,
pubmed-meshheading:7690249-Recombinant Fusion Proteins,
pubmed-meshheading:7690249-Regulatory Sequences, Nucleic Acid,
pubmed-meshheading:7690249-Ribosomal Protein S6,
pubmed-meshheading:7690249-Ribosomal Protein S6 Kinases,
pubmed-meshheading:7690249-Ribosomal Proteins,
pubmed-meshheading:7690249-Sequence Deletion,
pubmed-meshheading:7690249-Serum Response Factor,
pubmed-meshheading:7690249-Subcellular Fractions,
pubmed-meshheading:7690249-Transcription, Genetic,
pubmed-meshheading:7690249-Transcription Factors,
pubmed-meshheading:7690249-Tumor Cells, Cultured
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pubmed:year |
1993
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pubmed:articleTitle |
Activation of the early growth response 1 gene and nuclear pp90rsk in human myeloid leukemia cells by 1-(beta-D-arabinofuranosyl)cytosine.
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pubmed:affiliation |
Laboratory of Clinical Pharmacology, Dana-Farber Cancer Institute, Boston, Massachusetts.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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