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TGFbeta1/Smad3 coun...
TGFbeta1/Smad3 counteracts BRCA1-dependent repair of DNA damage
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- Dubrovska, Anna (författare)
- Uppsala universitet,Ludwiginstitutet för cancerforskning
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- Kanamoto, Takashi (författare)
- Uppsala universitet,Ludwiginstitutet för cancerforskning
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- Lomnytska, Marta (författare)
- Uppsala universitet,Ludwiginstitutet för cancerforskning
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- Heldin, Carl-Henrik (författare)
- Uppsala universitet,Ludwiginstitutet för cancerforskning
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Volodko, Natalya (författare)
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- Souchelnytskyi, Serhiy (författare)
- Karolinska Institutet,Uppsala universitet,Ludwiginstitutet för cancerforskning
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(creator_code:org_t)
- 2005-02-14
- 2005
- Engelska.
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Ingår i: Oncogene. - : Springer Science and Business Media LLC. - 0950-9232 .- 1476-5594. ; 24:14, s. 2289-2297
- Relaterad länk:
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https://www.nature.c...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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http://kipublication...
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Abstract
Ämnesord
Stäng
- 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.
Nyckelord
- Blotting; Western
- Cell Line
- Cell Survival
- DNA Damage
- DNA Repair/*physiology
- DNA-Binding Proteins/*physiology
- Genes; BRCA1
- Humans
- Immunohistochemistry
- Immunoprecipitation
- Research Support; Non-U.S. Gov't
- Trans-Activators/*physiology
- Transcription; Genetic
- Transforming Growth Factor beta/*physiology
- MEDICINE
- MEDICIN
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Oncogene
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