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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
6
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pubmed:dateCreated |
2005-3-16
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pubmed:abstractText |
The hSNF5 subunit of human SWI/SNF ATP-dependent chromatin remodeling complexes is a tumor suppressor that is inactivated in malignant rhabdoid tumors (MRTs). Here, we report that loss of hSNF5 function in MRT-derived cells leads to polyploidization and chromosomal instability. Re-expression of hSNF5 restored the coupling between cell cycle progression and ploidy checkpoints. In contrast, cancer-associated hSNF5 mutants harboring specific single amino acid substitutions exacerbated poly- and aneuploidization, due to abrogated chromosome segregation. We found that hSNF5 activates the mitotic checkpoint through the p16INK4a-cyclinD/CDK4-pRb-E2F pathway. These results establish that poly- and aneuploidy of tumor cells can result from mutations in a chromatin remodeler.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/15769941-10463572,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15769941-10521299,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15769941-10556283,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15769941-10739763,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15769941-10854417,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15769941-11095756,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15769941-11263494,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15769941-11283620,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15769941-11313485,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15769941-11756559,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15769941-11790558,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15769941-12045097,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15769941-12082626,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15769941-12138206,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15769941-12149641,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15769941-12226744,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15769941-12382173,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15769941-12450796,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15769941-12473340,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15769941-12573439,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15769941-12939745,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15769941-14604992,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15769941-14708009,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15769941-14729968,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15769941-14767597,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15769941-14964309,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15769941-14990991,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15769941-15023343,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15769941-15101046,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15769941-15306814,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15769941-15549096,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15769941-15627498,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15769941-9671307,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15769941-9892189
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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 |
Mar
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pubmed:issn |
0890-9369
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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 |
665-70
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:15769941-Amino Acid Substitution,
pubmed-meshheading:15769941-Cell Line,
pubmed-meshheading:15769941-Chromatin Assembly and Disassembly,
pubmed-meshheading:15769941-Chromosomal Instability,
pubmed-meshheading:15769941-Chromosomal Proteins, Non-Histone,
pubmed-meshheading:15769941-Cytogenetic Analysis,
pubmed-meshheading:15769941-DNA-Binding Proteins,
pubmed-meshheading:15769941-Fluorescent Antibody Technique,
pubmed-meshheading:15769941-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:15769941-Genes, Tumor Suppressor,
pubmed-meshheading:15769941-Humans,
pubmed-meshheading:15769941-In Situ Hybridization, Fluorescence,
pubmed-meshheading:15769941-Mitosis,
pubmed-meshheading:15769941-Mutagenesis,
pubmed-meshheading:15769941-Mutation,
pubmed-meshheading:15769941-Polyploidy,
pubmed-meshheading:15769941-Rhabdoid Tumor,
pubmed-meshheading:15769941-Signal Transduction,
pubmed-meshheading:15769941-Transcription Factors
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pubmed:year |
2005
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pubmed:articleTitle |
Cancer-associated mutations in chromatin remodeler hSNF5 promote chromosomal instability by compromising the mitotic checkpoint.
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pubmed:affiliation |
Department of Molecular and Cell Biology, Leiden University Medical Centre, 2300 RA Leiden, The Netherlands.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, Non-U.S. Gov't
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