Source:http://linkedlifedata.com/resource/pubmed/id/18372912
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
32
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pubmed:dateCreated |
2008-7-24
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pubmed:abstractText |
Id-1 (Inhibitor of DNA binding/differential-1) plays a positive role in tumorigenesis through regulation of multiple signaling pathways. Recently, it is suggested that upregulation of Id-1 in cancer cells promotes chromosomal instability. However, the underlying molecular mechanism is not known. In this study, we report a novel function of Id-1 in regulation of mitosis through physical interaction with Cdc20 (cell division cycle protein 20) and Cdh1 (Cdc20 homolog 1). During early mitosis, Id-1 interacts with Cdc20 and RASSF1A (Ras association domain family 1A), leading to enhanced APC(Cdc20) activity, which in turn promotes cyclin B1/securin degradation and premature mitosis. During late mitosis, Id-1 binds to Cdh1 and disrupts the interaction between Cdh1 and APC, resulting in suppression of APC(Cdh1) activity. On the other hand, overexpression of Cdh1 leads to Id-1 protein degradation, suggesting that Id-1 may also act as a substrate of APC(Cdh1). The negative effect of Id-1 on APC(Cdh1) results in suppression of APC(Cdh1)-induced Aurora A and Cdc20 degradation, leading to failure in cytokinesis. As a result, overexpression of Id-1 in human prostate epithelial cells leads to polyploidy in response to microtubule disruption, and this effect is abolished when Id-1 expression is suppressed using antisense technology. These results demonstrate a novel function of Id-1 in promoting chromosomal instability through modification of APC/C activity during mitosis and provide a novel molecular mechanism accounted for the function of Id-1 as an oncogene.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/CCNB1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/CDC20 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Cell Cycle Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin B,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin B1,
http://linkedlifedata.com/resource/pubmed/chemical/Inhibitor of Differentiation...,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/RASSF1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Ubiquitin,
http://linkedlifedata.com/resource/pubmed/chemical/Ubiquitin-Protein Ligase Complexes,
http://linkedlifedata.com/resource/pubmed/chemical/anaphase-promoting complex,
http://linkedlifedata.com/resource/pubmed/chemical/aurora kinase
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
1476-5594
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:day |
24
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pubmed:volume |
27
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
4456-66
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pubmed:dateRevised |
2011-7-11
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pubmed:meshHeading |
pubmed-meshheading:18372912-Cell Cycle Proteins,
pubmed-meshheading:18372912-Cell Line,
pubmed-meshheading:18372912-Chromosomal Instability,
pubmed-meshheading:18372912-Cyclin B,
pubmed-meshheading:18372912-Cyclin B1,
pubmed-meshheading:18372912-G1 Phase,
pubmed-meshheading:18372912-Humans,
pubmed-meshheading:18372912-Inhibitor of Differentiation Protein 1,
pubmed-meshheading:18372912-Microtubules,
pubmed-meshheading:18372912-Mitosis,
pubmed-meshheading:18372912-Protein-Serine-Threonine Kinases,
pubmed-meshheading:18372912-Tumor Suppressor Proteins,
pubmed-meshheading:18372912-Ubiquitin,
pubmed-meshheading:18372912-Ubiquitin-Protein Ligase Complexes
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pubmed:year |
2008
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pubmed:articleTitle |
Id-1 promotes chromosomal instability through modification of APC/C activity during mitosis in response to microtubule disruption.
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pubmed:affiliation |
Cancer Biology Group, Department of Anatomy, Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China. xhwang@hkucc.hku.hk
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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