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Related Experiment Videos

BRCA1 physically and functionally interacts with ATF1.

Y Houvras1, M Benezra, H Zhang

  • 1Derald H. Ruttenberg Cancer Center and the Department of Medicine, Mount Sinai School of Medicine, New York, New York 10029, USA.

The Journal of Biological Chemistry
|August 18, 2000
PubMed
Summary
This summary is machine-generated.

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The BRCA1 gene, linked to breast and ovarian cancer, interacts with ATF1 to activate gene transcription. This discovery sheds light on BRCA1

Area of Science:

  • Molecular Biology
  • Cancer Genetics
  • Gene Regulation

Background:

  • BRCA1 is a tumor suppressor gene associated with hereditary breast and ovarian cancers.
  • The precise function of the BRCA1 protein, particularly its role in gene regulation, is not fully understood.
  • BRCA1 possesses distinct functional domains, including an N-terminal RING finger for protein interactions and a C-terminal BRCT domain involved in transcription.

Purpose of the Study:

  • To investigate the biochemical function of BRCA1, focusing on its potential role in transcriptional regulation.
  • To identify and characterize protein-protein interactions involving the BRCA1 RING finger domain.
  • To determine if BRCA1 influences the activity of transcription factors and their target genes.

Main Methods:

Related Experiment Videos

  • Yeast two-hybrid system to screen for interacting proteins with the BRCA1 RING finger.
  • In vitro binding assays, yeast, and human cell co-immunoprecipitation to confirm physical association.
  • Transient transfection assays using reporter genes with cAMP response elements and natural promoters (e.g., TNF-alpha).

    • Main Results:

    • Identified a direct interaction between the BRCA1 RING finger and ATF1, a member of the CREB/ATF transcription factor family.
    • Demonstrated physical association between BRCA1 and ATF1 in vitro, in yeast, and in human cells.
    • Showed that BRCA1 stimulates transcription from cAMP response element-driven reporter genes and the natural TNF-alpha promoter.

    Conclusions:

    • BRCA1 physically interacts with the ATF1 transcription factor.
    • BRCA1 plays a role in transcriptional activation, specifically enhancing the activity of ATF1 target genes.
    • These findings suggest a role for BRCA1 in the transcriptional response to DNA damage through its interaction with ATF1.