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rdf:type |
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lifeskim:mentions |
umls-concept:C0033684,
umls-concept:C0041341,
umls-concept:C0079427,
umls-concept:C0086418,
umls-concept:C0208973,
umls-concept:C1325410,
umls-concept:C1517892,
umls-concept:C1521991,
umls-concept:C1571580,
umls-concept:C1704222,
umls-concept:C1704259,
umls-concept:C1704666,
umls-concept:C1705987
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pubmed:issue |
24
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pubmed:dateCreated |
2004-6-7
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pubmed:abstractText |
Tuberin (TSC2) is a tumor suppressor gene. At the cellular level, tuberin is required as a critical regulator of cell growth, neuronal differentiation, and tumor suppression. Here we report a critical role for tuberin in late stage myeloid cell differentiation. Tuberin strongly augments transforming growth factor (TGF)-beta1 signal transduction pathways, including SMAD activation. We also demonstrate that the amino-terminal region of tuberin interacts specifically with the MH2 domain of SMAD2 and SMAD3 proteins to regulate TGF-beta1-responsive genes such as p21(CIP). Inhibition of tuberin expression by Tsc2 antisense greatly reduces the ability of TGF-beta to transcriptionally regulate p21(CIP), p27(KIP), and cyclin A leading to an abrogation of the antiproliferative effects of TGF-beta1. Also, inhibition of tuberin expression during stimulation of monocytic differentiation with vitamin D(3) and TGF-beta1 significantly impaired myeloid cell growth inhibition and differentiation. Together, the data demonstrate the presence of a novel activation process following TGF-beta1 stimulation that requires tuberin-dependent activity.
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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/Cholecalciferol,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Repressor Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/SMAD2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/SMAD3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Smad2 Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Smad3 Protein,
http://linkedlifedata.com/resource/pubmed/chemical/TGFB1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators,
http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor beta,
http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor beta1,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/tuberous sclerosis complex 2 protein
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
11
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pubmed:volume |
279
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
25605-13
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:15066998-Binding Sites,
pubmed-meshheading:15066998-Cell Cycle,
pubmed-meshheading:15066998-Cell Differentiation,
pubmed-meshheading:15066998-Cell Line,
pubmed-meshheading:15066998-Cholecalciferol,
pubmed-meshheading:15066998-DNA-Binding Proteins,
pubmed-meshheading:15066998-Genes, Tumor Suppressor,
pubmed-meshheading:15066998-Humans,
pubmed-meshheading:15066998-Repressor Proteins,
pubmed-meshheading:15066998-Signal Transduction,
pubmed-meshheading:15066998-Smad2 Protein,
pubmed-meshheading:15066998-Smad3 Protein,
pubmed-meshheading:15066998-Trans-Activators,
pubmed-meshheading:15066998-Transcriptional Activation,
pubmed-meshheading:15066998-Transforming Growth Factor beta,
pubmed-meshheading:15066998-Transforming Growth Factor beta1,
pubmed-meshheading:15066998-Tumor Suppressor Proteins
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pubmed:year |
2004
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pubmed:articleTitle |
Tuberous sclerosis complex 2 gene product interacts with human SMAD proteins. A molecular link of two tumor suppressor pathways.
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pubmed:affiliation |
Basic Research Program, SAIC-Frederick, NCI-Frederick, Frederick, Maryland 21702, USA. birchena@mail.ncifcrf.gov
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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