| An E-box-mediated increase in cad transcription at the G1/S-phase boundary is suppressed by inhibitory c-Myc mutants. | |
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MedLine Citation:
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PMID: 7739536 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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To better understand the signaling pathways which lead to DNA synthesis in mammalian cells, we have studied the transcriptional activation of genes needed during the S phase of the cell cycle. Transcription of the gene encoding a pyrimidine biosynthetic enzyme, carbamoyl-phosphate synthase (glutamine-hydrolyzing)/aspartate carbamoyltransferase/dihydroorotase (cad), increases at the G1/S-phase boundary. We have mapped the growth-dependent response element in the hamster cad gene to the extended palindromic E-box sequence, CCACGTGG, which is centered at +65 in the 5' untranslated sequence. Mutation of the E box abolished growth-dependent transcription, and an oligonucleotide corresponding to the cad sequence at +55 to +75 (+55/+75) restored growth-dependent regulation to nonresponsive cad promoter mutants when placed down-stream of the transcription start site. The same oligonucleotide conferred less G1/S-phase induction when placed upstream of basal promoter elements. An analogous oligonucleotide containing the mutant E box had no effect in either location. Nuclear proteins bound the cad +55/+75 element in a cell cycle-dependent manner in electromobility shift assays; antibodies specific to USF and Max blocked the DNA-binding activity of different growth-regulated protein-DNA complexes. Expression of c-Myc mutants which have been shown to dominantly interfere with the function of c-Myc and Max significantly inhibited cad transcription during S phase but had no effect on transcription from another G1/S-phase-activated promoter, dhfr. These data support a model whereby E-box-binding proteins activate serum-induced transcription from the cad promoter at the G1/S-phase boundary and suggest that a Max-associated protein complex contributes to the serum response. |
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Authors:
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R J Miltenberger; K A Sukow; P J Farnham |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Molecular and cellular biology Volume: 15 ISSN: 0270-7306 ISO Abbreviation: Mol. Cell. Biol. Publication Date: 1995 May |
Date Detail:
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Created Date: 1995-06-02 Completed Date: 1995-06-02 Revised Date: 2009-11-18 |
Medline Journal Info:
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Nlm Unique ID: 8109087 Medline TA: Mol Cell Biol Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 2527-35 Citation Subset: IM |
Affiliation:
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McArdle Laboratory for Cancer Research, University of Wisconsin-Madison Medical School 53706, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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3T3 Cells Animals Aspartate Carbamoyltransferase / genetics* Base Sequence Binding Sites / genetics Carbamoyl-Phosphate Synthase (Glutamine-Hydrolyzing) / genetics* Cricetinae DNA / genetics, metabolism Dihydroorotase / genetics* G1 Phase / genetics Genes, myc* Mesocricetus Mice Molecular Sequence Data Multienzyme Complexes / genetics* Mutation Promoter Regions, Genetic S Phase / genetics Suppression, Genetic Transcription, Genetic |
| Grant Support | |
ID/Acronym/Agency:
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CA07175/CA/NCI NIH HHS; CA09135/CA/NCI NIH HHS; CA59524/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/CAD trifunctional enzyme; 0/Multienzyme Complexes; 9007-49-2/DNA; EC 2.1.3.2/Aspartate Carbamoyltransferase; EC 3.5.2.3/Dihydroorotase; EC 6.3.5.5/Carbamoyl-Phosphate Synthase (Glutamine-Hydrolyzing) |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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