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Title

Identification of BARD1 as mediator between proapoptotic stress and p53-dependent apoptosis

Authors
Leung, W C.
Harb, J.
Jefford, C E.
Soriano, Jesus
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Published in Molecular Cell. 2001, vol. 8, no. 6, p. 1255-66
Abstract The BRCA1-associated protein BARD1 is a putative tumor suppressor. We suggest that BARD1 is a mediator of apoptosis since (1) cell death in vivo (ischemic stroke) and in vitro is accompanied by increased levels of BARD1 protein and mRNA; (2) overexpression of BARD1 induces cell death with all features of apoptosis; and (3) BARD1-repressed cells are defective for the apoptotic response to genotoxic stress. The proapoptotic activity of BARD1 involves binding to and elevations of p53. BRCA1 is not required for but partially counteracts apoptosis induction by BARD1. A tumor-associated mutation Q564H of BARD1 is defective in apoptosis induction, thus suggesting a role of BARD1 in tumor suppression by mediating the signaling from proapoptotic stress toward induction of apoptosis.
Keywords AnimalsApoptosis/drug effects/radiation effectsBRCA1 Protein/genetics/metabolismBrain Ischemia/genetics/metabolism/pathologyCarrier Proteins/antagonists & inhibitors/chemistry/genetics/metabolismCell LineDNA Damage/drug effects/genetics/radiation effectsDoxorubicin/pharmacologyGene Expression/drug effects/radiation effectsGenes, Tumor SuppressorHela CellsHumansHypoxia, Brain/genetics/metabolism/pathologyInfarction, Middle Cerebral ArteryMiceMice, Inbred C57BLMolecular Sequence DataMutagens/pharmacologyMutation/geneticsProtein BindingRNA, Messenger/genetics/metabolismStroke/genetics/metabolism/pathologyTumor Suppressor Protein p53/biosynthesis/genetics/metabolismTumor Suppressor ProteinsUbiquitin-Protein LigasesUltraviolet RaysUp-Regulation/drug effects/radiation effects
Identifiers
PMID: 11779501
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IRMINGER, Irmgard et al. Identification of BARD1 as mediator between proapoptotic stress and p53-dependent apoptosis. In: Molecular Cell, 2001, vol. 8, n° 6, p. 1255-66. https://archive-ouverte.unige.ch/unige:3863

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Deposited on : 2009-10-22

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