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rdf:type |
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lifeskim:mentions |
umls-concept:C0021469,
umls-concept:C0022567,
umls-concept:C0037083,
umls-concept:C0040690,
umls-concept:C0086418,
umls-concept:C0205307,
umls-concept:C0376558,
umls-concept:C0442027,
umls-concept:C1710082,
umls-concept:C1711300,
umls-concept:C2700613
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pubmed:issue |
16
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pubmed:dateCreated |
2010-8-20
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pubmed:abstractText |
We previously demonstrated that Bmi-1 extended the in vitro life span of normal human oral keratinocytes (NHOK). We now report that the prolonged life span of NHOK by Bmi-1 is, in part, due to inhibition of the TGF-beta signaling pathway. Serial subculture of NHOK resulted in replicative senescence and terminal differentiation and activation of TGF-beta signaling pathway. This was accompanied with enhanced intracellular and secreted TGF-beta1 levels, phosphorylation of Smad2/3, and increased expression of p15(INK4B) and p57(KIP2). An ectopic expression of Bmi-1 in NHOK (HOK/Bmi-1) decreased the level of intracellular and secreted TGF-beta1 induced dephosphorylation of Smad2/3, and diminished the level of p15(INK4B) and p57(KIP2). Moreover, Bmi-1 expression led to the inhibition of TGF-beta-responsive promoter activity in a dose-specific manner. Knockdown of Bmi-1 in rapidly proliferating HOK/Bmi-1 and cancer cells increased the level of phosphorylated Smad2/3, p15(INK4B), and p57(KIP2). In addition, an exposure of senescent NHOK to TGF-beta receptor I kinase inhibitor or anti-TGF-beta antibody resulted in enhanced replicative potential of cells. Taken together, these data suggest that Bmi-1 suppresses senescence of cells by inhibiting the TGF-beta signaling pathway in NHOK.
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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/BMI1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/CDKN1A protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase Inhibitor...,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase Inhibitor...,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase Inhibitor...,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase Inhibitor...,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
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/Transforming Growth Factor beta1
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
1090-2422
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pubmed:author |
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pubmed:copyrightInfo |
Published by Elsevier Inc.
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pubmed:issnType |
Electronic
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pubmed:day |
1
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pubmed:volume |
316
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2600-8
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pubmed:dateRevised |
2011-10-3
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pubmed:meshHeading |
pubmed-meshheading:20630502-Blotting, Western,
pubmed-meshheading:20630502-Cell Aging,
pubmed-meshheading:20630502-Cell Proliferation,
pubmed-meshheading:20630502-Cell Survival,
pubmed-meshheading:20630502-Cells, Cultured,
pubmed-meshheading:20630502-Cyclin-Dependent Kinase Inhibitor p15,
pubmed-meshheading:20630502-Cyclin-Dependent Kinase Inhibitor p16,
pubmed-meshheading:20630502-Cyclin-Dependent Kinase Inhibitor p21,
pubmed-meshheading:20630502-Cyclin-Dependent Kinase Inhibitor p57,
pubmed-meshheading:20630502-Enzyme-Linked Immunosorbent Assay,
pubmed-meshheading:20630502-Gene Expression,
pubmed-meshheading:20630502-Genetic Vectors,
pubmed-meshheading:20630502-Humans,
pubmed-meshheading:20630502-Keratinocytes,
pubmed-meshheading:20630502-Mouth Mucosa,
pubmed-meshheading:20630502-Nuclear Proteins,
pubmed-meshheading:20630502-Phosphorylation,
pubmed-meshheading:20630502-Proto-Oncogene Proteins,
pubmed-meshheading:20630502-RNA, Messenger,
pubmed-meshheading:20630502-Repressor Proteins,
pubmed-meshheading:20630502-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:20630502-Signal Transduction,
pubmed-meshheading:20630502-Smad2 Protein,
pubmed-meshheading:20630502-Smad3 Protein,
pubmed-meshheading:20630502-Transfection,
pubmed-meshheading:20630502-Transforming Growth Factor beta1
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pubmed:year |
2010
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pubmed:articleTitle |
Bmi-1 extends the life span of normal human oral keratinocytes by inhibiting the TGF-beta signaling.
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pubmed:affiliation |
UCLA School of Dentistry, Center for the Health Sciences, Room 43-091, 10833 Le Conte Ave, Los Angeles, CA 90095, USA. rkim@dentistry.ucla.edu
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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