Expression of human nuclear receptors in plants for the discovery of plant-derived ligands.
Plants have the potential to produce a wide array of secondary metabolites that have utility as drugs to treat human diseases. To tap this potential, functional human nuclear receptors have been expressed in plants to create in planta screening assays as a tool to discover natural product ligands. Assays have been designed and validated using 3 nuclear receptors: the estrogen receptor (ER), the androgen receptor (AR), and the heterodimeric retinoid X receptor-alpha plus thyroid hormone receptor-beta (RXRA/THRB). Nuclear receptor-reporter constructs have been expressed in plants to detect the presence of natural ligands that are produced de novo in several plant species during different stages of development, in various tissues, and in response to different stress elicitors. Screening experiments with ER, AR, and RXRA/THRB have been conducted, leading to the identification of plant sources of natural product ligands of human nuclear receptors. This in planta screen has led to the identification of previously unreported ER ligands, providing evidence of the complementary value of this approach to current in vitro high-throughput screening assays.
Doukhanina
Elena V
EV
Ceres, Inc., Thousand Oaks, CA 91320, USA.
Apuya
Nestor R
NR
Yoo
Hye-Dong
HD
Wu
Chuan-Yin
CY
Davidow
Patricia
P
Krueger
Shannon
S
Flavell
Richard B
RB
Hamilton
Richard
R
Bobzin
Steven C
SC
D017360:Arabidopsis / Q000235:genetics / Q000382:microbiology; D031675:Eschscholzia / Q000235:genetics; D015870:Gene Expression; D006801:Humans; D008024:Ligands; D010944:Plants / Q000235:genetics / Q000378:metabolism*; D030821:Plants, Genetically Modified; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics* / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism; D012231:Rhizobium; D014026:Nicotiana / Q000235:genetics / Q000382:microbiology; D019076:Transgenes / Q000235:genetics*
D008024:Ligands; D018160:Receptors, Cytoplasmic and Nuclear; D011960:Receptors, Estrogen