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BRCA1 function mediates a TRAP/DRIP complex through direct interaction with TRAP220

Oncogene volume 23, pages 6000–6005 (2004)Cite this article

A Retraction to this article was published on 06 February 2014

Abstract

Breast cancer susceptibility gene 1 (BRCA1) is a tumor suppressor gene mutated in a high percentage of hereditary breast and ovarian cancers. The multifunctional BRCA1 protein acts on cell cycle control, exerting several highly specialized DNA repair processes through diverse domains. Gene regulation through its C-terminal domain (BRCT) is indispensable for BRCA1-mediated tumor suppression, suggesting the possibility that the BRCT domain interacts with co-regulator complexes. Using a biochemical approach with HeLa S3 nuclear extracts, we isolated BRCT-associated complexes and identified one of the purified components as TRAP220. We then performed interaction studies in vivo (co-immunoprecipitation) and in vitro (glutathione S-transferase pull-down assays) and showed that BRCT directly interacted with TRAP220. This in vitro interaction was completely abolished by BRCT point mutations typical of those found in patients with BRCA1 that lack transactivation function. BRCA1 transactivation function was dependent on TRAP220 expression level in a transient expression assay. Moreover, a cell survival assay showed that antisense TRAP220 expression to disrupt endogenous TRAP220 expression significantly reduced the survival rate potentiated by BRCA1 after DNA damage. These results suggested that a TRAP220 complex play an important role as putative co-activator complexes in BRCA1-mediated tumor suppression.

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Abbreviations

BRCA1:

breast cancer susceptibility gene 1

GST:

glutathione S-transferase

CMV:

cytomegalovirus

AdMLP:

adenovirus major late promoter

NR:

nuclear receptor

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Acknowledgements

We thank H Kitagawa and S Takezawa for helpful discussion and H Higuchi for manuscript preparation. This work was supported in part by grants-in-aid for priority areas from the Ministry of Education, Science, Sports, and Culture of Japan (to SK).

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Authors and Affiliations

  1. Institute of Molecular and Cellular Biosciences, University of Tokyo, Yayoi 1-1-1, Bunkyo-ku, Tokyo, 113-0034, Japan

    Osamu Wada, Hajime Oishi, Ichiro Takada, Junn Yanagisawa, Tetsu Yano & Shigeaki Kato

  2. Department of Obstetrics and Gynecology, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo, 113-8655, Japan

    Osamu Wada & Hajime Oishi

  3. SORST, Japan Science and Technology, Honcho 4-1-8, Kawaguchi, Saitama, 332-0012, Japan

    Ichiro Takada, Junn Yanagisawa & Shigeaki Kato

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  1. Osamu Wada
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Correspondence to Tetsu Yano.

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Wada, O., Oishi, H., Takada, I. et al. BRCA1 function mediates a TRAP/DRIP complex through direct interaction with TRAP220. Oncogene 23, 6000–6005 (2004). https://doi.org/10.1038/sj.onc.1207786

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Keywords

  • BRCA1
  • TRAP220
  • breast cancer

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