Interorganellar cooperation maintained via exquisitely controlled retrograde-signaling pathways is an evolutionary necessity for maintenance of cellular homeostasis. This signaling feature has therefore attracted much research attention aimed at improving understanding of the nature of these communication signals, how the signals are sensed, and ultimately the mechanism by which they integrate targeted processes that collectively culminate in organellar cooperativity. The answers to these questions will provide insight into how retrograde-signal-mediated regulatory mechanisms are recruited and which biological processes are targeted, and will advance our understanding of how organisms balance metabolic investments in growth against adaptation to environmental stress. This review summarizes the present understanding of the nature and the functional complexity of retrograde signals as integrators of interorganellar communication and orchestrators of plant development, and offers a perspective on the future of this critical and dynamic area of research.

Cellular homeostasis in response to internal and external stimuli requires a tightly coordinated interorgannellar communication network. We recently identified methylerythritol cyclodiphosphate (MEcPP) as a novel stress-specific retrograde signaling metabolite that accumulates in response to environmental perturbations to relay information from plastids to the nucleus. We now demonstrate, using a combination of transcriptome and proteome profiling approaches, that mutant plants (ceh1) with high endogenous levels of MEcPP display increased transcript and protein levels for a subset of the core unfolded protein response (UPR) genes. The UPR is an adaptive cellular response conserved throughout eukaryotes to stress conditions that perturb the endoplasmic reticulum (ER) homeostasis. Our results suggest that MEcPP directly triggers the UPR. Exogenous treatment with MEcPP induces the rapid and transient induction of both the unspliced and spliced forms of the UPR gene bZIP60. Moreover, compared with the parent background (P), ceh1 mutants are less sensitive to the ER-stress-inducing agent tunicamycin (Tm). P and ceh1 plants treated with Tm display similar UPR transcript profiles, suggesting that although MEcPP accumulation causes partial induction of selected UPR genes, full induction is triggered by accumulation of misfolded proteins. This finding refines our perspective of interorgannellar communication by providing a link between a plastidial retrograde signaling molecule and its targeted ensemble of UPR components in ER.T he endoplasmic reticulum (ER) function is crucial to adjustment and maintenance of a balance between protein loads and folding capacity in response to frequently changing intracellular and environmental conditions. To maintain balance (homeostasis) under stressful conditions, the ER activates conserved intracellular signal transduction pathways collectively termed the unfolded protein response (UPR) (1). The UPR monitors ER protein-folding capacity and communicates the ER status to gene expression programs that up-regulate genes encoding components of the protein folding machinery or the ER-associated degradation system (1, 2). In plants, two distinct and parallel branches of the UPR signaling pathway have been identified. One pathway involves two integral membrane-bound transcription factors (bZIP17 and bZIP28). The other pathway involves an ER membrane-localized dual-functioning (kinase/ribonuclease) protein, inositol-requiring protein-1 (IRE1). IRE1 catalyzes unconventional cytoplasmic splicing of mRNA encoding basic leucine zipper 60 (bZIP60), the transcription factor responsible for the induction of ER quality control genes (3, 4). Stress causes activation and nuclear relocation of bZIP17 and bZIP28, and activation of IRE1 responsible for splicing of bZIP60 mRNA that encodes transcriptionally active nuclear localized bZIP60. These activated transcription factors induce transcription of target genes, including genes that mediate the UPR.Protein folding is coupled to many biological processes,...

Taken together, USP7 is a promising therapeutic target and USP7 inhibitors hold promise as a new approach to cancer therapy.

Maintaining nitric oxide (NO) homeostasis is essential for normal plant physiological processes. However, very little is known about the mechanisms of NO modulation in plants. Here, we report a unique mechanism for the catabolism of NO based on the reaction with the plant hormone cytokinin. We screened for NO-insensitive mutants in Arabidopsis and isolated two allelic lines, cnu1-1 and 1-2 (continuous NO-unstressed 1), that were identified as the previously reported altered meristem program 1 (amp1) and as having elevated levels of cytokinins. A double mutant of cnu1-2 and nitric oxide overexpression 1 (nox1) reduced the severity of the phenotypes ascribed to excess NO levels as did treating the nox1 line with trans-zeatin, the predominant form of cytokinin in Arabidopsis. We further showed that peroxinitrite, an active NO derivative, can react with zeatin in vitro, which together with the results in vivo suggests that cytokinins suppress the action of NO most likely through direct interaction between them, leading to the reduction of endogenous NO levels. These results provide insights into NO signaling and regulation of its bioactivity in plants.is one of the most widespread signaling molecules in living organisms (1, 2). In plants, NO is involved in the regulation of numerous physiological processes during growth and development and is also an important modulator of disease resistance (2-4). Several laboratories discovered that NO is produced not only from nitrate/nitrite but also from L-arginine (L-Arg), which is the main substrate for NO synthesis in animals (4-6). NO is also a widespread atmospheric pollutant. Therefore, this gas not only is a pivotal player in signal transduction but also has the potential to exert significant deleterious effects by being a pollutant. As an inevitable result, increased NO levels in the atmosphere can influence multiple NO-regulated processes in organisms. Despite the wealth of information gathered from analyses of NO functioning in plants, the molecular processes underlying NO effects in plants are still largely unknown.NO differs from other signaling molecules by being reactive, lipophilic, and volatile. In fact, chemically, NO is a free radical, and such a reactive molecule is unlikely to interact specifically with a single specific receptor (3). In animals, NO appears to act through the chemical modification of targets. NO can bind to transition metals of metalloproteins (metal nitrosylation). It also can bind covalently to cysteine (S-nitrosylation) and tyrosine (tyrosine nitration) residues (3,7,8). Such specific protein modifications are emerging as key mechanistic intermediates for NO signal transduction. In plant cells, NO has also been found to regulate the activity of various target proteins through S-or metal-nitrosylation and probably through tyrosine nitration as well (9-13).Furthermore, it has been shown that NO takes part in different phytohormone signaling pathways, frequently under the control of hormonal stimuli. For instance, NO functions in auxin-induc...

Highlight2-C-Methyl-D-erythritol cyclopyrophosphate is an isoprenoid intermediate and a dynamic plastidial stress-specific signal that calibrates salicylic acid–jasmonic acid crosstalk and induces jasmonic acid-responsive genes in the presence of high salicylic acid in a manner dependent on the F-box protein COI1.