BRCA1 transcriptional activity is enhanced by interactions between its AD1 domain and AhR View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2008-11

AUTHORS

Hyo Jin Kang, Hee Jeong Kim, Chi-Heum Cho, Yanfen Hu, Rong Li, Insoo Bae

ABSTRACT

PURPOSE: We previously reported that BRCA1 interacts with aryl hydrocarbon receptor nuclear translocator (ARNT) and that this interaction affects TCDD-induced CYP1A1 gene expression (Kang et al., J Biol Chem 281:14654-14662, 2006). In this study we continue this investigation and begin to define the significance of this interaction for the regulation of stress-induced transcription. METHODS: Immunoprecipitations (IPs), western blot (WB) analysis, GST pull-down assays and promoter reporter assays were used to investigate whether the aryl hydrocarbon receptor (AhR) can regulate transcription that is dependent on the activation domain 1 (AD1) domain of BRCA1. RESULTS: We show that AhR, a transcription factor, can bind specifically to AD1 in the C-terminal region of BRCA1 and affect BRCA1's ability to regulate transcription activity. We found that xenobiotics that positively and negatively affect AhR's activity as a transcription factor (e.g., dioxin and alpha-naphthoflavone, respectively), have similar effects on AhR's ability to affect AD1-domain-dependent transcription. These physical and functional AhR-AD1 interactions may require the coiled-coil motif in AD1 because point-mutations in this motif reduce these interactions. CONCLUSION: Xenobiotic-activated AhR can function in two ways, as a component of the AhR/ARNT transcription factor and a regulator of AD1-dependent transcription. Consequently, BRCA1 has two distinct mechanisms for sensing xenobiotics and regulating AhR-dependent stress responses to these xenobiotics. We speculate that the normal functioning of this interaction could play a role in BRCA1's tumor suppressing ability. More... »

PAGES

965-975

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s00280-008-0686-x

DOI

http://dx.doi.org/10.1007/s00280-008-0686-x

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1029324697

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/18259752


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