Expression of caveolin-1 in the human mammary adenocarcinoma cell line MCF-7 causes ligand-independent concentration of oestrogen receptor α (ERα) in the nucleus, and potentiates ligand-independent and ligand-dependent transcription from an oestrogen response element-driven reporter gene. Furthermore, caveolin-1 co-immunoprecipitates with ERα [Schlegel, Wang, Katzenellenbogen, Pestell and Lisanti (1999) J. Biol. Chem. 274, 33551–33556]. In the present study we show that caveolin-1 binds directly to ERα. This interaction is mediated by residues 82–101 of caveolin-1 (i.e. the caveolin scaffolding domain) and residues 1–282 of ERα. The caveolin-binding domain of ERα includes the ligand-independent transactivation domain, activation function (AF)-1, but lacks the hormone-binding domain and the ligand-gated transactivation domain, AF-2. In co-transfection studies, caveolin-1 potentiates the transcriptional activation of ERα(1–282), a truncation mutant that has intact AF-1 and DNA-binding domains. Since AF-1 activity is regulated largely by phosphorylation we determined that co-expression with caveolin-1 increased the basal phosphorylation of ERα(1–282), but blocked the epidermal growth factor-dependent increase in phosphorylation. Indeed, caveolin-1 interacted with and potentiated the transactivation of an ERα mutant that cannot be phosphorylated by extracellular signal-regulated kinase (ERK)1/2 [ERα(Ser118 → Ala)]. Thus caveolin-1 is a novel ERα regulator that drives ERK1/2-independent phosphorylation and activation of AF-1.
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October 2001
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Research Article|
September 24 2001
Ligand-independent activation of oestrogen receptor α by caveolin-1
Amnon SCHLEGEL;
Amnon SCHLEGEL
∗Department of Molecular Pharmacology, The Albert Einstein Cancer Centre, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, U.S.A.
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Chenguang WANG;
Chenguang WANG
†Department of Developmental and Molecular Biology, The Albert Einstein Cancer Centre, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, U.S.A.
‡Department of Medicine, The Albert Einstein Cancer Centre, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, U.S.A.
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Richard G. PESTELL;
Richard G. PESTELL
†Department of Developmental and Molecular Biology, The Albert Einstein Cancer Centre, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, U.S.A.
‡Department of Medicine, The Albert Einstein Cancer Centre, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, U.S.A.
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Michael P. LISANTI
Michael P. LISANTI
1
∗Department of Molecular Pharmacology, The Albert Einstein Cancer Centre, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, U.S.A.
1To whom correspondence should be addressed (e-mail lisanti@aecom.yu.edu).
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Publisher: Portland Press Ltd
Received:
April 04 2001
Revision Received:
July 02 2001
Accepted:
July 24 2001
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London ©2001
2001
Biochem J (2001) 359 (1): 203–210.
Article history
Received:
April 04 2001
Revision Received:
July 02 2001
Accepted:
July 24 2001
Citation
Amnon SCHLEGEL, Chenguang WANG, Richard G. PESTELL, Michael P. LISANTI; Ligand-independent activation of oestrogen receptor α by caveolin-1. Biochem J 1 October 2001; 359 (1): 203–210. doi: https://doi.org/10.1042/bj3590203
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