Linked Life Data

15077185

Source:http://linkedlifedata.com/resource/pubmed/id/15077185

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
20
pubmed:dateCreated
2004-4-29
pubmed:abstractText
The tumor suppressor protein BARD1 plays a dual role in response to genotoxic stress: DNA repair as a BARD1-BRCA1 heterodimer and induction of apoptosis in a BRCA1-independent manner. We have constructed a series of BARD1 deletion mutants and analysed their cellular distribution and capacity to induce apoptosis. As opposed to previous studies suggesting an exclusively nuclear localization of BARD1, we found, both in tissues and cell cultures, nuclear and cytoplasmic localization of BARD1. Enhanced cytoplasmic localization of BARD1, as well as appearance of a 67 kDa C-terminal proteolytic cleavage product, coincided with apoptosis. BARD1 translocates to the nucleus independently of BRCA1. For recruitment to nuclear dots, however, the BRCA1-interacting RING finger domain is required but not sufficient. Protein levels of N-terminal RING finger deletion mutants were much higher than those of full-length BARD1, despite comparable mRNA levels, suggesting that the N-terminal region comprising the RING finger is important for BARD1 degradation. Sequences required for apoptosis induction were mapped between the ankyrin repeats and the BRCT domains coinciding with two known cancer-associated missense mutations. We suggest that nuclear and cytoplasmic localization of BARD1 reflect its dual function and that the increased cytoplasmic localization of BARD1 is associated with apoptosis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0950-9232
pubmed:author
pubmed:issnType
Print
pubmed:day
29
pubmed:volume
23
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3509-20
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Nuclear-cytoplasmic translocation of BARD1 is linked to its apoptotic activity.
pubmed:affiliation
Biology of Aging Laboratory, Department of Geriatrics, University of Geneva, 1225 Geneva, Switzerland.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't