The nuclear BAG-1 isoform, BAG-1L, enhances oestrogen-dependent transcription

Ramsey I. Cutress, Paul A. Townsend, Adam Sharp, Anna Maison, Lynn Wood, Ron Lee, Matthew Brimmell, Mark A. Mullee, Peter W M Johnson, Gavin T. Royle, Adrian C. Bateman, Graham Packham

    Research output: Contribution to journalArticlepeer-review


    BAG-1 is a multifunctional protein that interacts with a wide range of cellular targets including heat-shock proteins and some nuclear hormone receptors. BAG-1 exists as three major isoforms, BAG-1L, BAG-1M and BAG-1S. BAG-1L contains a nuclear localization signal, which is not present in the other isoforms, and is predominantly localized in the cell nucleus. Here we have investigated the effects of BAG-1 on function of the oestrogen receptor (ER), a key growth control molecule and target for hormonal therapy in breast cancer. We demonstrate that BAG-1L, but not BAG-1S or BAG-1M, increased oestrogen-dependent transcription in breast cancer cells. BAG-1L interacted with and stimulated the activity of both ER α and β. Although BAG-1L and ERs colocalize to the nucleus, fusing BAG-1S to an heterologous nuclear localization sequence was not sufficient to stimulate transcription. Consistent with an important effect on receptor function, nuclear BAG-1 expression in breast cancers was associated with expression of the progesterone receptor, a transcriptional target of ERα, and was associated with improved survival in patients treated with hormonal therapy. These data suggest that BAG-1L is an important determinant of ER function in vitro and in human breast cancer.
    Original languageEnglish
    Pages (from-to)4973-4982
    Number of pages9
    Issue number32
    Publication statusPublished - 7 Aug 2003


    • BAG-1
    • Breast cancer
    • Hormone therapy
    • Oestrogen
    • Receptor
    • Survival


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