Linked Life Data

18071904

Source:http://linkedlifedata.com/resource/pubmed/id/18071904

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2008-1-30
pubmed:abstractText
BRCA1 acts as a tumor suppressor gene, and germ-line mutations in this gene are found in a large proportion of families with breast and ovarian cancers. The BRCA1 protein has been implicated in several cellular processes, such as transcription regulation, DNA responses to DNA damage signals, cell cycle control, and apoptosis. Apoptosis plays a critical role in radiation- and chemotherapy-induced cytotoxicity, and its impairment contributes to resistance to tumor treatments. In an attempt to elucidate the role of BRCA1 in apoptosis, we examined the response to chemotherapeutic drugs of cells expressing physiological levels of BRCA1 protein. We showed that chemotherapy-induced apoptosis leads to a caspase-mediated cleavage of BRCA1. We then showed that the BRCA1-p90 cleavage product is mainly localized in the cytoplasm. Finally, we demonstrated that cancer-associated mutations affecting the BRCT tandem repeat abolish its pro-apoptotic function. The data presented here provide new insight into the role of endogenous BRCA1 as a mediator of apoptosis and show that BRCA1 functions as a molecular determinant of response to a range of cytotoxic chemotherapeutic agents.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1360-8185
pubmed:author
pubmed:issnType
Print
pubmed:volume
13
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
237-46
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Caspase-dependent BRCA1 cleavage facilitates chemotherapy-induced apoptosis.
pubmed:affiliation
Génétique Moléculaire Signalisation et Cancer, Université de Lyon, Lyon 69373, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't