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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
3
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pubmed:dateCreated |
2006-8-11
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pubmed:abstractText |
Cellular senescence is a stable state of proliferative arrest that provides a barrier to malignant transformation and contributes to the antitumor activity of certain chemotherapies. Senescent cells can accumulate senescence-associated heterochromatic foci (SAHFs), which may provide a chromatin buffer that prevents activation of proliferation-associated genes by mitogenic transcription factors. Surprisingly, we show that the High-Mobility Group A (HMGA) proteins, which can promote tumorigenesis, accumulate on the chromatin of senescent fibroblasts and are essential structural components of SAHFs. HMGA proteins cooperate with the p16(INK4a) tumor suppressor to promote SAHF formation and proliferative arrest and stabilize senescence by contributing to the repression of proliferation-associated genes. These antiproliferative activities are canceled by coexpression of the HDM2 and CDK4 oncogenes, which are often coamplified with HMGA2 in human cancers. Our results identify a component of the senescence machinery that contributes to heterochromatin formation and imply that HMGA proteins also act in tumor suppressor networks.
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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/CDK4 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase 4,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase Inhibitor...,
http://linkedlifedata.com/resource/pubmed/chemical/HMGA Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/HMGA2 Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Heterochromatin,
http://linkedlifedata.com/resource/pubmed/chemical/MDM2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-mdm2,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Proteins
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0092-8674
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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 |
126
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
503-14
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:16901784-Animals,
pubmed-meshheading:16901784-Cell Aging,
pubmed-meshheading:16901784-Cell Line,
pubmed-meshheading:16901784-Cell Nucleus,
pubmed-meshheading:16901784-Cell Proliferation,
pubmed-meshheading:16901784-Cell Transformation, Neoplastic,
pubmed-meshheading:16901784-Cells, Cultured,
pubmed-meshheading:16901784-Cyclin-Dependent Kinase 4,
pubmed-meshheading:16901784-Cyclin-Dependent Kinase Inhibitor p16,
pubmed-meshheading:16901784-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:16901784-HMGA Proteins,
pubmed-meshheading:16901784-HMGA2 Protein,
pubmed-meshheading:16901784-Heterochromatin,
pubmed-meshheading:16901784-Humans,
pubmed-meshheading:16901784-Mice,
pubmed-meshheading:16901784-Proto-Oncogene Proteins c-mdm2,
pubmed-meshheading:16901784-Transcriptional Activation,
pubmed-meshheading:16901784-Tumor Suppressor Proteins
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pubmed:year |
2006
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pubmed:articleTitle |
A novel role for high-mobility group a proteins in cellular senescence and heterochromatin formation.
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pubmed:affiliation |
Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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