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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
24
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pubmed:dateCreated |
2001-2-8
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pubmed:abstractText |
Smad3 is a key signal transducer of transforming growth factor-ss (TGF-ss) and activin, and is known to be a DNA-binding transcriptional regulator. Here we report a novel property of Smad3 in regulating the proteasomal degradation of the human enhancer of filamentation 1 (HEF1), which is a member of the Cas family of cytoplasmic docking proteins. Our studies revealed that Smad3 interacts with HEF1 and triggers the proteasomal degradation of HEF1 in overexpression systems. In addition, TGF-ss stimulation induces rapid proteasomal degradation of endogenous HEF1 in different TGF-ss-responsive cell lines. Interestingly, the degradation of HEF1 protein in epithelial cells is followed closely by an increase in HEF1 mRNA, resulting in a time-dependent increase in HEF1 protein level in TGF-ss-treated cells. Furthermore, we observed that an elevated HEF1 protein level inhibits TGF-ss-induced Smad3-mediated gene responses. These data provide the first evidence for a novel cytoplasmic activity of Smad3 in regulating proteasomal degradation of HEF1 and also suggest a role for HEF1 in a negative feedback mechanism of the TGF-ss signaling pathway.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/11118211-10455189,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11118211-10531062,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11118211-10535941,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11118211-10660041,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11118211-10675905,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11118211-10887155,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11118211-1372641,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11118211-8047140,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11118211-8272871,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11118211-8395914,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11118211-8425219,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11118211-8622651,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11118211-8668148,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11118211-8879209,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11118211-9020138,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11118211-9162067,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11118211-9497377,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11118211-9584194,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11118211-9597127,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11118211-9606191,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11118211-9759503,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11118211-9865691
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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/Adaptor Proteins, Signal Transducing,
http://linkedlifedata.com/resource/pubmed/chemical/Cysteine Endopeptidases,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Luciferases,
http://linkedlifedata.com/resource/pubmed/chemical/Multienzyme Complexes,
http://linkedlifedata.com/resource/pubmed/chemical/NEDD9 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proteasome Endopeptidase Complex,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/SMAD3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Smad3 Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators,
http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor beta
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0261-4189
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
19
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
6759-69
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:11118211-Adaptor Proteins, Signal Transducing,
pubmed-meshheading:11118211-Cell Line,
pubmed-meshheading:11118211-Cysteine Endopeptidases,
pubmed-meshheading:11118211-DNA-Binding Proteins,
pubmed-meshheading:11118211-Epithelial Cells,
pubmed-meshheading:11118211-Gene Expression Regulation,
pubmed-meshheading:11118211-Genes, Reporter,
pubmed-meshheading:11118211-Humans,
pubmed-meshheading:11118211-Luciferases,
pubmed-meshheading:11118211-Multienzyme Complexes,
pubmed-meshheading:11118211-Phosphoproteins,
pubmed-meshheading:11118211-Proteasome Endopeptidase Complex,
pubmed-meshheading:11118211-Recombinant Proteins,
pubmed-meshheading:11118211-Saccharomyces cerevisiae,
pubmed-meshheading:11118211-Signal Transduction,
pubmed-meshheading:11118211-Smad3 Protein,
pubmed-meshheading:11118211-Trans-Activators,
pubmed-meshheading:11118211-Transcription, Genetic,
pubmed-meshheading:11118211-Transforming Growth Factor beta
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pubmed:year |
2000
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pubmed:articleTitle |
A novel ability of Smad3 to regulate proteasomal degradation of a Cas family member HEF1.
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pubmed:affiliation |
Department of Surgery, Massachusetts General Hospital and Department of Genetics, Harvard Medical School, Boston, MA 02114, 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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