Year: 2001
Type: article
Abstract: Expression of caveolin-1 in the human mammary adenocarcinoma cell line MCF-7 causes ligand-independent concentration of oestrogen receptor alpha (ERalpha) 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 ERalpha [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 ERalpha. This interaction is mediated by residues 82-101 of caveolin-1 (i.e. the caveolin scaffolding domain) and residues 1-282 of ERalpha. The caveolin-binding domain of ERalpha 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 ERalpha(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 ERalpha(1-282), but blocked the epidermal growth factor-dependent increase in phosphorylation. Indeed, caveolin-1 interacted with and potentiated the transactivation of an ERalpha mutant that cannot be phosphorylated by extracellular signal-regulated kinase (ERK)1/2 [ERalpha(Ser(118)-->Ala)]. Thus caveolin-1 is a novel ERalpha regulator that drives ERK1/2-independent phosphorylation and activation of AF-1.
Source: Biochemical Journal
Authors: Amnon SCHLEGEL, Chenguang WANG, Richard G. PESTELL, Michael P. LISANTI
Institution: Albert Einstein College of Medicine
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: bronze
Awards: G1124166624, G1383220726, G1624074299, Medical Scientist Training Program, G2460367380, G4442243157, ANTIPROGESTINS AND ACTIVE CELL DEATH IN BREAST CANCER, Androgen Receptor Function in Prostate Cancer, Initiation and Maintenance in Mammary Tumorigenesis, G7158444836, G9000038118, G9000158551
OpenAlex ID: W2056595592