Estrogen receptor, a common interaction partner for a subset of nuclear receptors.
Nuclear receptors regulate transcription by binding to specific DNA response elements as homodimers or heterodimers. Herein, the yeast and mammalian two-hybrid tests as well as glutathione-S-transferase pull-down assays were exploited to demonstrate that estrogen receptor (ER) directly binds to a subset of nuclear receptors through protein-protein interactions between ligand-binding domains. These receptors include hepatocyte nuclear factor 4, thyroid hormone receptor (TR), retinoic acid receptor (RAR), ERbeta, and retinoid X receptor (RXR). In yeast cells, a LexA fusion protein to the human ER ligand-binding domain (LexA/ER-LBD) was an inert transactivator of a LacZ reporter gene controlled by upstream LexA-binding sites. However, LexA/ER-LBD differentially modulated the LacZ reporter gene expression when coexpressed with native TRs, RARs, or RXRs. Similarly, cotransfection of these receptors in CV1 cells up- or down-regulated transactivations by ER. From these results, we propose that ER is a common interaction partner for a subset of receptors, and these interactions should mediate novel signaling pathways in vivo.
Lee
S K
SK
College of Pharmacy, Chonnam National University, Kwangju, Korea.
Choi
H S
HS
Song
M R
MR
Lee
M O
MO
Lee
J W
JW
D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D001665:Binding Sites; D004268:DNA-Binding Proteins; D051557:Hepatocyte Nuclear Factor 4; D006801:Humans; D010750:Phosphoproteins / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D011988:Receptors, Thyroid Hormone / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D047488:Retinoid X Receptors; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D015003:Yeasts / Q000235:genetics; D001616:beta-Galactosidase / Q000235:genetics / Q000378:metabolism; D000099160:LexA Repressor Protein
D001426:Bacterial Proteins; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins; D051557:Hepatocyte Nuclear Factor 4; D010750:Phosphoproteins; D018160:Receptors, Cytoplasmic and Nuclear; D011960:Receptors, Estrogen; D018168:Receptors, Retinoic Acid; D011988:Receptors, Thyroid Hormone; D011994:Recombinant Proteins; D047488:Retinoid X Receptors; D012697:Serine Endopeptidases; D014157:Transcription Factors; D001616:beta-Galactosidase; D000099160:LexA Repressor Protein; C403128:MLX protein, human