The genes that control mammalian programmed cell death are conserved across wide evolutionary distances. Although plant cells can undergo apoptosis-like cell death, plant homologs of mammalian regulators of apoptosis have, in general, not been found. This is in part due to the lack of primary sequence conservation between animal and putative plant regulators of apoptosis. Thus, alternative approaches beyond sequence similarities are required to find functional plant homologs of apoptosis regulators. Here, we present the results of using advanced bioinformatic tools to uncover the Arabidopsis family of BAG proteins. The mammalian BAG (Bcl-2-associated athanogene) proteins are a family of chaperone regulators that modulate a number of diverse processes ranging from proliferation to growth arrest and cell death. Such proteins are distinguished by a conserved BAG domain that directly interacts with Hsp70 and Hsc70 proteins to regulate their activity. Our searches of the Arabidopsis thaliana genome sequence revealed seven homologs of the BAG protein family. We further show that plant BAG family members are also multifunctional and remarkably similar to their animal counterparts, as they regulate apoptosis-like processes ranging from pathogen attack to abiotic stress and development. Programmed cell death (PCD)2 plays an indispensable role in development and physiology, but it is unclear whether the mechanisms governing PCD in both plants and animals are similar. The genes that control programmed cell death are conserved across wide evolutionary distances from Caenorhabditis elegans to humans (1), although whether such conservation extends to plants is unknown. PCD plays a normal physiological role in many plant processes, and although the biochemical mechanisms responsible for cell suicide in plants are largely unknown, a number of reports suggest similarities to animal PCD (reviewed in Ref. 2). Moreover, ectopic expression of certain animal anti-apoptotic genes in transgenic plants is known to confer protection from pathogens and other stresses by death suppression (3-5).The identification of homologs of animal cell death regulators is of considerable interest. However, to date, few endogenous plant genes that show significant sequence similarity to animal apoptotic genes have been identified. Examination of the completed genome sequence of Arabidopsis thaliana, as well as other partially or nearly complete plant genomes by tools such as BLAST and FASTA, has not revealed any apparent homologs to the core apoptosis regulators. This may be explained by high sequence divergence of functional plant homologs of animal apoptotic proteins. Therefore, one approach to identify candidate PCD modulators in plants is through advanced tools of bioinformatics. We describe the results of such efforts, viz. the identification and characterization of the BAG protein family of Arabidopsis by profilesequence (Pfam) and profile-profile (FFAS) algorithms.The BAG proteins are an evolutionarily conserved family of multifunctional proteins...

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-α plus thyroid hormone receptor-β (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)