Linked Life Data

18372912

Source:http://linkedlifedata.com/resource/pubmed/id/18372912

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
32
pubmed:dateCreated
2008-7-24
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
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
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1476-5594
pubmed:author
pubmed:issnType
Electronic
pubmed:day
24
pubmed:volume
27
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4456-66
pubmed:dateRevised
2011-7-11
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Id-1 promotes chromosomal instability through modification of APC/C activity during mitosis in response to microtubule disruption.
pubmed:affiliation
Cancer Biology Group, Department of Anatomy, Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China. xhwang@hkucc.hku.hk
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't