Tamoxifen-Bound Estrogen Receptor (ER) Strongly Interacts with the Nuclear Matrix Protein HET/SAF-B, a Novel Inhibitor of ER-Mediated Transactivation

Autor: Michaelis M, Zhang Q, Davie, Steffi Oesterreich, Zhao Hh, C K Osborne, Suzanne A. W. Fuqua, Torsten A. Hopp, Adrian V. Lee
Rok vydání: 2000
Předmět:
Transcriptional Activation
Carcinoma
Hepatocellular
Neoplasms
Hormone-Dependent
animal structures
Macromolecular Substances
Recombinant Fusion Proteins
Molecular Sequence Data
Estrogen receptor
Bone Neoplasms
Breast Neoplasms
Plasma protein binding
Adenocarcinoma
Biology
Structure-Activity Relationship
Transactivation
Endocrinology
Estrogen Receptor Modulators
Nuclear Matrix-Associated Proteins
Chlorocebus aethiops
Tumor Cells
Cultured
Animals
Humans
Nuclear protein
Binding site
Molecular Biology
Transcription factor
Osteosarcoma
Base Sequence
Estradiol
Liver Neoplasms
fungi
Nuclear Proteins
DNA
Matrix Attachment Region Binding Proteins
General Medicine
Antiestrogen
Nuclear matrix
Molecular biology
Neoplasm Proteins
Protein Structure
Tertiary
DNA-Binding Proteins
Tamoxifen
Receptors
Estrogen
Depression
Chemical
COS Cells
Female
Protein Binding
Zdroj: Molecular Endocrinology. 14:369-381
ISSN: 1944-9917
0888-8809
DOI: 10.1210/mend.14.3.0432
Popis: The estrogen receptor (ER) is a ligand-dependent transcription factor that acts in a cell- and promoter-specific manner. Evidence suggests that the activity of the ER can be regulated by a number of other stimuli (e.g. growth factors) and that the effects of the ER are modulated by nuclear factors termed coregulators. While the interplay among these factors may in part explain the pleiotropic effects elicited by the ER, there are several other less well described mechanisms of control, such as interactions with the nuclear matrix. Here we report that the nuclear matrix protein/scaffold attachment factor HET/SAF-B is an ER-interacting protein. ER and HET/SAF-B interact in in vitro binding assays, with HET binding to both the ER DNA-binding domain and the hinge region. Coimmunoprecipitation experiments reveal that HET/SAF-B and ER associate in cell lines in the presence or absence of estradiol, but binding is increased by the antiestrogen tamoxifen. HET/SAF-B enhances tamoxifen antagonism of estrogen-induced ER-mediated transactivation, but at high concentrations can inhibit both estrogen and tamoxifen-induced ER activity. HET/SAF-B-mediated repression of ER activity is dependent upon interaction with the ER-DBD. While the existence of high-affinity binding sites for the ER in the nuclear matrix has been known for some time, we now provide evidence of a specific nuclear matrix protein binding to the ER. Furthermore, our data showing that HET/SAF-B binds to ER particularly strongly in the presence of tamoxifen suggests that it may be important for the antagonist effect of tamoxifen.
Databáze: OpenAIRE
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