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Journal of Biomolecular Screening, Vol. 12, No. 3, 385-395 (2007)
DOI: 10.1177/1087057107299255

Expression of Human Nuclear Receptors in Plants for the Discovery of Plant-Derived Ligands

Elena V. Doukhanina

Ceres, Inc. 1535 Rancho Conejo Boulevard Thousand Oaks, CA 91320

Nestor R. Apuya

Ceres, Inc. 1535 Rancho Conejo Boulevard Thousand Oaks, CA 91320, napuya{at}ceres-inc.com

Hye-Dong Yoo

Ceres, Inc. 1535 Rancho Conejo Boulevard Thousand Oaks, CA 91320

Chuan-Yin Wu

Ceres, Inc. 1535 Rancho Conejo Boulevard Thousand Oaks, CA 91320

Patricia Davidow

Ceres, Inc. 1535 Rancho Conejo Boulevard Thousand Oaks, CA 91320

Shannon Krueger

Ceres, Inc. 1535 Rancho Conejo Boulevard Thousand Oaks, CA 91320

Richard B. Flavell

Ceres, Inc. 1535 Rancho Conejo Boulevard Thousand Oaks, CA 91320

Richard Hamilton

Ceres, Inc. 1535 Rancho Conejo Boulevard Thousand Oaks, CA 91320

Steven C. Bobzin

Ceres, Inc. 1535 Rancho Conejo Boulevard Thousand Oaks, CA 91320

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 receptorß (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. (Journal of Biomolecular Screening 2007:385-395)

Key Words: in planta screening • natural products • ligands • nuclear receptors


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