JAZ Genes Research Articles

Mining for Meaning: Visualization Approaches to DecipheringArabidopsisStress Responses in Roots and Shoots

Massive amounts of transcriptomic data documenting plant responses to changes in environment continue to accumulate in online databases. Unfortunately, many of these data sets have not been analyzed in full detail, especially those that involve time course experiments. To gain more knowledge of the successive gene expression events that occur when stress is initiated in one organ and then relayed to another, we have chosen stress response data for Arabidopsis shoots and roots from the detailed time course study of Killian et al. as a promising source to mine. Using refined statistical analysis, modified vector analysis, and a GO enrichment algorithm, more information was revealed concerning the effects of salt and UVB on gene expression events in shoots and roots over a 24-h time period. GeneMania, with in-house modifications, was used to further analyze abscisic acid (ABA) and jasmonic acid-related (JA) gene expression events in salt-stressed roots and shoots. JA effects appeared to be quite distinct in roots when compared to shoots, especially with respect to the expression of members of the negative regulatory JAZ gene family. In contrast, ABA-related gene expression events were more similar in the two organs. Instances of crosstalk between hormones were observed, as were early responses of regulatory genes involved in both auxin and cytokinin signaling. In the case of each hormone class examined, hormone biosynthesis genes were coexpressed with the genes encoding negative regulators of the corresponding signaling pathway. Hypotheses to explain this finding and future experiments to further explore these nonlinear phenomena are proposed.

Alternative splicing expands the repertoire of dominant JAZ repressors of jasmonate signaling

Jasmonates (JAs) are fatty acid-derived signaling compounds that control diverse aspects of plant growth, development and immunity. The F-box protein COI1 functions both as a receptor for jasmonoyl-l-isoleucine (JA-Ile) and as the component of an E3-ubiquitin ligase complex (SCF(COI1) ) that targets JAZ transcriptional regulators for degradation. A key feature of JAZ proteins is the C-terminal Jas motif that mediates the JA-Ile-dependent interaction with COI1. Here, we show that most JAZ genes from evolutionarily diverse plants contain a conserved intron that splits the Jas motif into 20 N-terminal and seven C-terminal (X(5) PY) amino acid submotifs. In most members of the Arabidopsis JAZ family, alternative splicing events involving retention of this intron generate proteins that are truncated before the X(5) PY sequence. In vitro pull-down and yeast two-hybrid assays indicate that these splice variants have reduced capacity to form stable complexes with COI1 in the presence of the bioactive stereoisomer of the hormone (3R,7S)-JA-Ile. cDNA overexpression studies showed that some, but not all, truncated splice variants are dominant repressors of JA signaling. We also show that strong constitutive expression of an intron-containing JAZ10 genomic clone is sufficient to repress JA responses. These findings provide evidence for functional differences between JAZ isoforms, and establish a direct link between the alternative splicing of JAZ pre-mRNA and the dominant repression of JA signal output. We propose that production of dominant JAZ repressors by alternative splicing reduces the negative consequences associated with inappropriate or hyperactivation of the JA response pathway.

Structure‐based JAZ ligand‐J1 and its analogues show strong cytotoxic effects on glioma cells in vitro ‐ A new class of glioma therapy drugs?

Hypoxia/ischemia and oxidative stress has been shown to be involved in glioma tumorigenesis. The Jaz gene encodes a zinc finger protein that can respond to oxidative stress with increased expression both in vitro and in vivo. We have previously reported that JAZ exhibits a tumor grade‐dependent increased expression in gliomas with the highest levels in GBM and shows increased cytoplasm‐nuclear translocation adjacent to pseudopalisading necrosis. We hypothesized that JAZ plays a role in glioma tumorigenesis. Targeting JAZ with a molecular docking approach, we identified one small molecule compound named “J1” that exhibited strong dose‐ and time‐dependent glioma cytotoxic effects in vitro (human U87MG, U118MG, A172, and mouse GL261 glioma cell lines) with GI50 around 25microM. Several known J1 analogues also displayed differential glioma killing effects. Flow cytometry showed that J1 led to cell cycle arrest. Quantitative proteomic analysis revealed that, in both U87MG and U118MG glioma cells, J1 treatment led to a significant decrease of PLOD2 (procollagen hydroxylase 2), which is known to be induced by hypoxia, associated with cancer progression, and was reported to be increased in pseudopalisading GBM cells. These results suggest that JAZ ligand J1 and its analogues have the potential to become a new class of chemotherapy drugs for glioma treatment.