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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
25
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pubmed:dateCreated |
1999-1-14
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pubmed:abstractText |
The human type VII collagen gene (COL7A1) recently has been identified as an immediate-early response gene for transforming growth factor beta (TGF-beta)/SMAD signaling pathway. In this study, by using MDA-MB-468 SMAD4-/- breast carcinoma cells, we demonstrate that expression of SMAD4 is an absolute requirement for SMAD-mediated promoter activity. We also demonstrate that the SMAD binding sequence (SBS) representing the TGF-beta response element in the region -496/-444 of the COL7A1 promoter functions as an enhancer in the context of a heterologous promoter. Electrophoretic mobility-shift assays with nuclear extracts from COS-1 cells transfected with expression vectors for SMADs 1-5 indicate that SMAD3 forms a complex with a migration similar to that of the endogenous TGF-beta-specific complex observed in fibroblast extracts. Electrophoretic mobility-shift assays using recombinant glutathione S-transferase-SMAD fusion proteins indicate that both SMAD4 and C-terminally truncated SMAD3, but not SMAD2, can bind the COL7A1 SBS. Coexpression of SMAD3 and SMAD4 in COS-1 cells leads to the formation of two complexes: a DNA/protein complex containing SMAD3 alone and another slower-migrating complex containing both SMAD3 and SMAD4, the latter complex not being detected in fibroblasts. Maximal transactivation of COL7A1 SBS-driven promoters in either MDA-MB-468 carcinoma cells or fibroblasts requires concomitant overexpression of SMAD3 and SMAD4. These data may represent the first identification of a functional homomeric SMAD3 complex regulating a human gene.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/9843964-2041787,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9843964-2170018,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9843964-4705382,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9843964-6960240,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9843964-8473327,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9843964-8595876,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9843964-8653691,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9843964-8663601,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9843964-8774881,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9843964-8893010,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9843964-8980228,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9843964-9092567,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9843964-9153220,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9843964-9215638,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9843964-9230443,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9843964-9288972,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9843964-9311995,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9843964-9335505,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9843964-9335507,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9843964-9372933,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9843964-9389648,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9843964-9393997,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9843964-9409665,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9843964-9436979,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9843964-9502724,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9843964-9582342,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9843964-9606191,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9843964-9618481,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9843964-9620846,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9843964-9670020,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9843964-9679056,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9843964-9679060,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9843964-9689110,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9843964-9694870,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9843964-9707553
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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 |
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0027-8424
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
8
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pubmed:volume |
95
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
14769-74
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:9843964-Animals,
pubmed-meshheading:9843964-COS Cells,
pubmed-meshheading:9843964-Collagen,
pubmed-meshheading:9843964-DNA-Binding Proteins,
pubmed-meshheading:9843964-Female,
pubmed-meshheading:9843964-Humans,
pubmed-meshheading:9843964-Lymphotoxin-alpha,
pubmed-meshheading:9843964-Promoter Regions, Genetic,
pubmed-meshheading:9843964-Signal Transduction,
pubmed-meshheading:9843964-Smad3 Protein,
pubmed-meshheading:9843964-Smad4 Protein,
pubmed-meshheading:9843964-Trans-Activators,
pubmed-meshheading:9843964-Transcriptional Activation,
pubmed-meshheading:9843964-Tumor Cells, Cultured
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pubmed:year |
1998
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pubmed:articleTitle |
SMAD3/4-dependent transcriptional activation of the human type VII collagen gene (COL7A1) promoter by transforming growth factor beta.
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pubmed:affiliation |
Department of Dermatology and Cutaneous Biology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107, 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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