Upadacitinib protects against cisplatin-induced renal and hepatic dysfunction without impairing its anticancer activity.

Cisplatin-induced renal and hepatic dysfunctions are major drawbacks and obstacles to its clinical applications. Induction of inflammation is a part of its molecular mechanism of toxicity. The impact of upadacitinib, a selective JAK1-inhibitory anti-inflammatory agent, on cisplatin-induced adverse effects, histopathologic changes, kidney and liver functions, oxidative stress, and inflammatory biomarkers were investigated compared to silymarin and losartan in male Wistar rats.

Regulation of Plant Cellular and Organismal Development by SUMO.

This chapter clearly demonstrates the breadth and spectrum of the processes that SUMO regulates during plant development. The gross phenotypes observed in mutants of the SUMO conjugation and deconjugation enzymes reflect these essential roles, and detailed analyses of these mutants under different growth conditions revealed roles in biotic and abiotic stress responses, phosphate starvation, nitrate and sulphur metabolism, freezing and drought tolerance and response to excess copper. SUMO functions also intersect with those regulated by several hormones such as salicylic acid , abscisic acid , gibberellins and auxin, and detailed studies provide mechanistic clues of how sumoylation may regulate these processes.

Analysis of Small Ubiquitin-Like Modifier (SUMO) Targets Reflects the Essential Nature of Protein SUMOylation and Provides Insight to Elucidate the Role of SUMO in Plant Development.

Posttranslational modification of proteins by small ubiquitin-like modifier (SUMO) has received much attention, reflected by a flood of recent studies implicating SUMO in a wide range of cellular and molecular activities, many of which are conserved throughout eukaryotes. Whereas most of these studies were performed in vitro or in single cells, plants provide an excellent system to study the role of SUMO at the developmental level. Consistent with its essential roles during plant development, mutations of the basic SUMOylation machinery in Arabidopsis (Arabidopsis thaliana) cause embryo stage arrest or major developmental defects due to perturbation of the dynamics of target SUMOylation.

Elevated salicylic acid levels conferred by increased expression of ISOCHORISMATE SYNTHASE 1 contribute to hyperaccumulation of SUMO1 conjugates in the Arabidopsis mutant early in short days 4.

Post-translational modification of proteins by attachment of small ubiquitin-like modifier (SUMO) is essential for plant growth and development. Mutations in the SUMO protease early in short days 4 (ESD4) cause hyperaccumulation of conjugates formed between SUMO and its substrates, and phenotypically are associated with extreme early flowering and impaired growth. We performed a suppressor mutagenesis screen of esd4 and identified a series of mutants called suppressor of esd4 (sed), which delay flowering, enhance growth and reduce hyperaccumulation of SUMO conjugates.

Extent and significance of non-covalent SUMO interactions in plant development.

Posttranslational modification of proteins by SUMO plays essential roles in plant growth and development. We, and others, have previously identified Arabidopsis proteins covalently modified by SUMO. In our recent report, we assessed the extent and significance of non-covalent SUMO interactions with plant proteins by using three Arabidopsis SUMO isoforms as baits in large-scale yeast two-hybrid screens.