Identification and characterization of the BEL1-like genes reveal their potential roles in plant growth and abiotic stress response in tomato.

BEL1-like (BELL) transcription factors, belonging to three-amino acid-loop-extension (TALE) superfamily, are ubiquitous in plants. BELLs regulate a wide range of plant biological processes, but the understanding of the BELL family in tomato (Solanum lycopersicum) remains fragmentary. In this study, a total of 14 members of the SlBELL family were identified in tomato. SlBELL proteins contained the conserved BELL and SKY domains that served as typical structures of the BELL family. Syntenic analysis indicated that the BELL orthologs between tomato and other dicots had close evolutionary relationships. Furthermore, the promoters of SlBELLs contained numerous cis-elements related to plant growth, development, and stress response. The SlBELL genes exhibited different tissue-specific expression profiles and responded to cold, heat, and drought stresses, implying their potential functions in regulating multiple aspects of plant growth, as well as in response to abiotic stresses. Through the interaction network prediction, we found that most SlBELL proteins displayed probable interactions with the KNOTTED1-like (KNOX) proteins, another kind of transcription factor in the TALE superfamily. These findings laid foundations for further dissection of the functions of SlBELL genes in tomato, as well as for exploration of the evolutionary relationships of BELL homologs among different plant species.

Identification and characterization of the CONSTANS (CO)/CONSTANS-like (COL) genes related to photoperiodic signaling and flowering in tomato.

CO is an important regulator of photoperiodic response and flowering. However, the biological functions of CO and COL genes in tomato (Solanum lycopersicum) remain elusive. Here we identified 13 members in CO/COL family from the tomato genome. They were divided into three groups, and each group had specific characteristics in gene structures and protein domains. The SlCO/SlCOL genes showed different tissue-specific expression patterns and circadian rhythms, indicating their functional diversity in tomato. Moreover, among 13 members, the expression of SlCOL, SlCOL4a, and SlCOL4b was negatively correlated with flowering time variation in ten tomato lines. Through interaction network prediction, we found three FLOWERING LOCUS T (FT) orthologs, SINGLE FLOWER TRUSS (SFT), FT-like (FTL), and FT-like 1 (FTL1), which functioned as candidate interactors of SlCOL, SlCOL4a, and SlCOL4b. Further expression analyses suggested that SFT coincided with the three SlCOL genes in ten tomato lines with varied flowering time. These findings implied that SlCOL, SlCOL4a, and SlCOL4b are potential flowering inducers in tomato, and SFT may act as their downstream target. Thus, our study built a foundation for understanding the precise roles of SlCO/SlCOL family in plant growth and development of tomato, especially in flowering.

SAR study of celastrol analogs targeting Nur77-mediated inflammatory pathway.

Nur77, an orphan member of the nuclear receptor superfamily, plays an important role in the regulation of inflammatory processes. Our previous work found that celastrol, a pentacyclic triterpene, bound to Nur77 to inhibit inflammation in a Nur77-dependent manner. Celastrol binding to Nur77 promotes Nur77 translocation from nucleus to cytoplasm, resulting in clearance of inflamed mitochondria and then alleviation of inflammation. Here, we report the design, synthesis, SAR study and biological evaluation of a series of celastrol analogs. A total of 24 celastrol derivatives were made. Compound 3a with a Kd of 0.87 µM was found to be less toxic than celastrol and could be a hit molecule for further optimization.

Celastrol binds to its target protein via specific noncovalent interactions and reversible covalent bonds.

Celastrol is one of the most studied natural products. Our studies show for the first time that celastrol can bind to its target protein via specific noncovalent interactions that position celastrol next to the thiol group of the reactive cysteine for reversible covalent bond formation. Such specific noncovalent interactions confer celastrol binding specificity and demonstrate the feasibility of improving the efficacy and selectivity of celastrol for therapeutic applications.

AlCl3·6H2O-Catalyzed Friedel-Crafts Alkylation of Indoles by the para-Quinone Methide Moiety of Celastrol.

A classical Friedel-Crafts alkylation of different indoles catalyzed by AlCl3·6H2O has been developed for a well-known important natural product, celastrol, resulting in a series of derivatives for further biological evaluation. The catalyst loading was reduced to 5 mol %, the reaction proceeds at ambient temperature and reaction time is only 3 h. The product yields range from 20% to 99%. A reaction mechanism is also proposed, based on our experiment results.