Biology subjects

Karapetyan, S.

Publications and source records attributed to Karapetyan, S..

5 recordsLinked to original sources

bioRxiv2026

Ca2+-activated CKL3 phosphorylates nucleoporin 58 to reprogram nuclear transport and execute effector-triggered immunity

Recognition of pathogen effectors by nucleotide-binding leucine-rich repeat receptors (NLRs) activates effector-triggered immunity (ETI) in plants through resistosome formation, which generates a sustained cytosolic Ca2+ influx and ultimately leads to programmed cell death (PCD) at infection sites and resistance. However, the mechanisms linking Ca2+ influx to ETI execution remains a major knowledge gap. Using TurboID proximity labeling with the central transport channel nucleoporin 58 (Nup58) as a probe, we show that, instead of deregulation, ETI induction restricts general nuclear trafficking while selectively enhancing nuclear import of defense-related proteins. This switch is driven by elevated cytosolic Ca2+, which binds to the conserved Asp-149 in CASEIN KINASE 1-LIKE 3 (CKL3), promoting its interaction with and phosphorylation of Nup58 at Ser-149, thereby altering nuclear pore selectivity. This study identifies CKL3 and Nup58 as key regulators of ETI by establishing a mechanistic link from resistosome-mediated Ca2+ influx to nuclear transport reprogramming and immune execution.

plant biology↗

bioRxiv2025

Primary metabolism determines the outcome of salicylic acid-mediated immune induction

Controlling the deleterious effects of immune responses is as vital as fighting infection. In plants, this is achieved, in part, by circadian clock-mediated regulation, such as the synthesis of and response to the immune hormone salicylic acid (SA)1,2. Application of SA at the same concentration under light/dark cycles induces immunity with minimal impact on growth, however, prolonged darkness leads to plant death2. To uncover what determines this life-or-death outcome, we identified twenty survival of SA-induced death (ssd) mutants through genetic screening. These mutants are defective in starch, glucose, and nitrate metabolism, and circadian regulation, and accumulate excessive starch and/or glucose. Likewise, glucose application rescues SA-treated plants in prolonged darkness. Surprisingly, SA treatment does not deplete glucose, but instead, induces amino acid and fatty acid catabolism. Through transcriptomic analyses of glucose-rescued WT plants and ssd mutants for shared pathways, we found that SA triggers plant death in darkness by inducing oxidative stress, and water loss, while glucose antagonizes these processes, boosts ER protein processing and re-establishes the anabolism-catabolism balance. Interestingly, the programmed cell death induced by effector-triggered immunity shares common transcriptomic patterns with those observed during SA-induced cell death in darkness and could also be attenuated by glucose treatment. Therefore, coordination with the cellular metabolic context plays a central role in determining immune outcomes and optimizing plant health.

plant biology↗

bioRxiv2025

Salicylic Acid Engages Central Metabolic Regulators SnRK1 and TOR to Govern Immunity by Differential Phosphorylation of NPR1

Immunity is a delicate balance between combating infection and preserving the metabolic functions vital for host survival. However, the mechanisms by which immune responses are coordinated with cellular metabolism remain largely unknown. Here, we show that NONEXPRESSER OF PR GENES 1 (NPR1), the central plant immune regulator of salicylic acid (SA)-mediated defense responses, is controlled by a cascade of posttranslational modifications (PTMs) involving two master nutrient-sensing kinases. Under normal growth conditions, TARGET OF RAPAMYCIN (TOR) inhibits NPR1 through phosphorylation at Ser-55/59. During defense responses, elevated SA enhances SNF1-RELATED KINASE 1 (SnRK1) activity, which in turn inhibits TOR signaling and phosphorylates NPR1 at Ser-557. This phosphorylation event activates NPR1 and facilitates its subsequent PTMs. Together, our results reveal an integral role of SA (the active metabolite of aspirin) in controlling central metabolic regulators SnRK1 and TOR to coordinate immune responses and growth through antagonistic modifications of NPR1.

plant biology↗

bioRxiv2023

Circadian redox rhythm gates immune-induced cell death distinctly from the genetic clock

Organisms use circadian clocks to synchronize physiological processes to anticipate the Earths day-night cycles and regulate responses to environmental stresses to gain competitive advantage1. While divergent genetic clocks have been studied extensively in bacteria, fungi, plants, and animals, a conserved circadian redox rhythm has only recently been reported and hypothesized to be a more ancient clock2, 3. However, it is controversial whether the redox rhythm serves as an independent clock and controls specific biological processes4. Here, we uncovered the coexistence of redox and genetic rhythms with distinct period lengths and transcriptional targets through concurrent metabolic and transcriptional time-course measurements in an Arabidopsis long-period clock mutant5. Analysis of the target genes indicated regulation of the immune-induced programmed cell death (PCD) by the redox rhythm. Moreover, this time-of-day-sensitive PCD was eliminated by redox perturbation and by blocking the signalling pathway of the plant defence hormones jasmonic acid/ethylene, while remaining intact in a genetic-clock-impaired line. We demonstrate that compared to robust genetic clocks, the more sensitive circadian redox rhythm serves as a signalling hub in regulating incidental energy-intensive processes, such as immune-induced PCD6, to provide organisms a flexible strategy to prevent metabolic overload caused by stress, a unique role for the redox oscillator.

plant biology↗

bioRxiv2020

Protein mimetic amyloid inhibitor potently abrogates cancer-associated mutant p53 aggregation and restores tumor suppressor function

Missense mutations in p53 are severely deleterious and occur in over 50% of all human cancers. The vast majority of these mutations are located in the inherently unstable DNA-binding domain (DBD), many of which destabilize the domain further and expose its aggregation-prone hydrophobic core, prompting self-assembly of mutant p53 into inactive cytosolic amyloid-like aggregates. Screening an oligopyridylamide library, previously shown to inhibit amyloid formation associated with Alzheimers disease and type II diabetes, identified a tripyridylamide, ADH-6, that potently abrogates self-assembly of the aggregation-nucleating subdomain of mutant p53 DBD. Moreover, ADH-6 effectively targets and dissociates mutant p53 aggregates in human cancer cells, which restores p53s transcriptional activity, leading to cell cycle arrest and apoptosis. Notably, ADH-6 treatment substantially shrinks xenografts harboring mutant p53 and prolongs survival, while exhibiting no toxicity to healthy tissue. This study demonstrates the first successful application of a bona fide small-molecule amyloid inhibitor as an anticancer agent.

cancer biology↗