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TGFbeta1/Smad3 coun...
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Dubrovska, AnnaUppsala universitet,Ludwiginstitutet för cancerforskning
(author)
TGFbeta1/Smad3 counteracts BRCA1-dependent repair of DNA damage
- Article/chapterEnglish2005
Publisher, publication year, extent ...
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2005-02-14
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Springer Science and Business Media LLC,2005
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printrdacarrier
Numbers
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LIBRIS-ID:oai:DiVA.org:uu-72687
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-72687URI
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https://doi.org/10.1038/sj.onc.1208443DOI
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http://kipublications.ki.se/Default.aspx?queryparsed=id:110979263URI
Supplementary language notes
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Language:English
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Summary in:English &language:-1_t
Part of subdatabase
Classification
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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Inactivation of the BRCA1 gene has been found to confer susceptibility to early-onset familial breast and ovarian cancers. BRCA1 regulates DNA repair, chromatin remodeling and affects gene transcription. Transforming growth factor-beta (TGFbeta) is a potent regulator of growth, apoptosis and invasiveness of tumor cells, including breast cancer cells. Here we show that Smad3 which is a component of the TGFbeta signaling pathway, forms a complex with BRCA1 in vitro and in vivo. The interaction is mediated by the MH1 domain of Smad3 and the C-terminal part of BRCA1. We observed a co-localization of Smad3 and BRCA1 in nuclear complexes. We also found that TGFbeta1/Smad3 counteracted BRCA1-dependent repair of DNA double-strand breaks in human breast epithelial cells, as evaluated by BRCA1 nuclear foci formation, single-cell gel electrophoresis and cell survival assays. Thus, TGFbeta1/Smad3 suppresses BRCA1-dependent DNA repair in response to a DNA damaging agent.
Subject headings and genre
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Blotting; Western
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Cell Line
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Cell Survival
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DNA Damage
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DNA Repair/*physiology
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DNA-Binding Proteins/*physiology
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Genes; BRCA1
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Humans
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Immunohistochemistry
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Immunoprecipitation
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Research Support; Non-U.S. Gov't
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Trans-Activators/*physiology
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Transcription; Genetic
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Transforming Growth Factor beta/*physiology
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MEDICINE
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MEDICIN
Added entries (persons, corporate bodies, meetings, titles ...)
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Kanamoto, TakashiUppsala universitet,Ludwiginstitutet för cancerforskning
(author)
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Lomnytska, MartaUppsala universitet,Ludwiginstitutet för cancerforskning(Swepub:uu)marlo829
(author)
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Heldin, Carl-HenrikUppsala universitet,Ludwiginstitutet för cancerforskning(Swepub:uu)carlheld
(author)
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Volodko, Natalya
(author)
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Souchelnytskyi, SerhiyKarolinska Institutet,Uppsala universitet,Ludwiginstitutet för cancerforskning(Swepub:uu)sergsouc
(author)
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Uppsala universitetLudwiginstitutet för cancerforskning
(creator_code:org_t)
Related titles
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In:Oncogene: Springer Science and Business Media LLC24:14, s. 2289-22970950-92321476-5594
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Oncogene
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