Project description:Gene expression profiles of WT, jaz9 and jaz10 mutant treated with mock or with 3, 6, or 8 was performed using the custom microarray Agilent-034592 The experiments were designed to explore the effect of antagonist of jasmonate perception in WT and two mutants
Project description:In plants, recognition of immunogenic molecular patterns, such as bacterial flagellin (flg22 epitope), leads to an enhanced state of immunity, designated pattern-triggered immunity (PTI). Following cognate ligand perception, pattern recognition receptors initiate sequential phosphorylation events to activate defense responses against invading pathogens. To gain further insight into PTI signaling, we conducted phosphoproteome analyses in Arabidopsis seedlings with immunogenic molecular patterns.
Project description:Clinical resistance such as androgen receptor (AR) mutation, AR overexpression, and AR splice variants (ARVs) restrict the second-generation antiandrogens benefit in patients with castration-resistant prostate cancer (CRPC). Several strategies have been implemented to develop novel antiandrogens to circumvent the occurring resistance. In this study, based on rational drug design, we discovered and identified a bifunctional small molecule Z15 as a potent AR antagonist and AR selective degrader. Z15 could directly bind to the AR ligand-binding domain (LBD) and inhibited DHT-induced AR nuclear translocation. Furthermore, Z15 promoted AR degradation through the proteasome pathway. As a result, our in vitro and in vivo studies showed Z15 efficiently suppressed AR and AR mutant transcription activity, downregulated mRNA and protein levels of AR target genes, as well as overcame AR LBD mutations, AR amplification, and ARVs-induced resistance in CRPC. In conclusion, our data illustrate the synergistic importance of AR antagonism and degradation in advanced prostate cancer treatment.
Project description:This study evaluates the transcriptome of Arabidopsis thaliana seedlings (Col-0 ecotype) treated with methyl jasmonate (MeJA) or with the salicylic acid analog benzothiadiazole (BTH).
Project description:RNA is emerging as a valuable target for the development of novel therapeutic agents. The rational design of RNA-targeting small molecules, however, has been hampered by the relative lack of methods for the analysis of small molecule-RNA interactions. Here we present our efforts to develop such a platform using photoaffinity labeling. This technique, termed Photoaffinity Evaluation of RNA Ligation-Sequencing (PEARL-seq), enables the rapid identification of small molecule binding locations within their RNA targets and can provide information on ligand selectivity across multiple different RNAs. These data, when supplemented with small molecule SAR data and RNA probing data enables the construction of a computational model of the RNA-ligand structure, thereby enabling the rational design of novel RNA-targeted ligands.
