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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
2002-3-6
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pubmed:abstractText |
Tumor suppressor Smad4 is the common signaling effector in the transforming growth factor beta (TGF-beta) superfamily. Phosphorylated regulatory Smads (R-Smads) interact with Smad4, and the complex translocates into the nucleus to regulate gene transcription. Proper TGF-beta signaling requires precise control of Smad functions. Smurfs have been shown to mediate the degradation of R-Smads but not the common-partner Smad4. We report a novel mechanism of Smad4 degradation. Jab1 interacts directly with Smad4 and induces its ubiquitylation for degradation. Jab1 was initially identified as a co-activator of c-Jun, and it also induces degradation of cell cycle inhibitor p27 and tumor suppressor p53. Ectopic expression of Jab1 decreased endogenous Smad4 steady-state levels. The 26S proteasome inhibitors lactacystin and MG132 reduced the degradation rate of Smad4 protein. Examination of the effects of JAB1-induced Smad4 degradation indicates that Jab1 inhibited TGF-beta-induced gene transcription. Our data suggest that Jab1 antagonizes TGF-beta function by inducing degradation of Smad4 through a distinct degradation pathway.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/11818334-10086358,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11818334-10220381,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11818334-10224145,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11818334-10340381,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11818334-10458166,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11818334-10660041,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11818334-10664585,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11818334-10781087,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11818334-10782111,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11818334-10819541,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11818334-10903862,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11818334-11016919,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11818334-11158580,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11818334-11223033,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11818334-11278251,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11818334-11285227,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11818334-11337587,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11818334-11337588,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11818334-7950318,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11818334-8553063,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11818334-8837781,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11818334-8939725,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11818334-9660945,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11818334-9682038,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11818334-9759503,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11818334-9789328,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11818334-9811788
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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 |
Feb
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pubmed:issn |
1469-221X
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
3
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
171-6
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
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pubmed:year |
2002
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pubmed:articleTitle |
Jab1 antagonizes TGF-beta signaling by inducing Smad4 degradation.
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pubmed:affiliation |
Department of Pathology, University of Alabama at Birmingham School of Medicine, 1670 University Boulevard, VH G002, Birmingham, AL 35294-0019, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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