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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
2004-7-9
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pubmed:abstractText |
BRCA1 mutations have long been associated with altered apoptosis. We have recently reported that caspase 3 activation is increased in human ovarian surface epithelial (OSE) cells expressing a germline N-terminal BRCA1 185delAG mutation. Here, we report increased caspase 3 activity in 185delAG OSE cells associated with decreased expression of cIAP-1 and X-linked inhibitor of apoptosis (XIAP), and decreased ubiquitination of caspase 3. Overexpression of XIAP restored active caspase 3 ubiquitination and lowered levels of caspase 3 activity. Further, the BRCA1 185delAG mutation was associated with reduced levels of phosphorylated Akt1. Transfection with activated Akt1 led to increased cIAP-1 and XIAP levels similar to that seen in BRCA1 185delAG cell lines. Taken together, these data suggest a direct link between the BRCA1 185delAG mutation and alterations in the caspase-mediated apoptotic pathway.
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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/AKT1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/BRCA1 Protein,
http://linkedlifedata.com/resource/pubmed/chemical/CASP3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Caspases,
http://linkedlifedata.com/resource/pubmed/chemical/Inhibitor of Apoptosis Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt,
http://linkedlifedata.com/resource/pubmed/chemical/Ubiquitin,
http://linkedlifedata.com/resource/pubmed/chemical/X-Linked Inhibitor of Apoptosis...,
http://linkedlifedata.com/resource/pubmed/chemical/XIAP protein, human
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0014-4827
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
298
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
9-16
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:15242757-Apoptosis,
pubmed-meshheading:15242757-BRCA1 Protein,
pubmed-meshheading:15242757-Carcinoma,
pubmed-meshheading:15242757-Caspase 3,
pubmed-meshheading:15242757-Caspases,
pubmed-meshheading:15242757-Down-Regulation,
pubmed-meshheading:15242757-Epithelial Cells,
pubmed-meshheading:15242757-Female,
pubmed-meshheading:15242757-Gene Expression Regulation, Enzymologic,
pubmed-meshheading:15242757-Humans,
pubmed-meshheading:15242757-Inhibitor of Apoptosis Proteins,
pubmed-meshheading:15242757-Mutation,
pubmed-meshheading:15242757-Ovarian Neoplasms,
pubmed-meshheading:15242757-Ovary,
pubmed-meshheading:15242757-Phosphorylation,
pubmed-meshheading:15242757-Protein-Serine-Threonine Kinases,
pubmed-meshheading:15242757-Proteins,
pubmed-meshheading:15242757-Proto-Oncogene Proteins,
pubmed-meshheading:15242757-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:15242757-Signal Transduction,
pubmed-meshheading:15242757-Ubiquitin,
pubmed-meshheading:15242757-X-Linked Inhibitor of Apoptosis Protein
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pubmed:year |
2004
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pubmed:articleTitle |
BRCA1 185delAG mutation inhibits Akt-dependent, IAP-mediated caspase 3 inactivation in human ovarian surface epithelial cells.
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pubmed:affiliation |
University of South Florida College, Tampa 33612, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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