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The protein kinase AvrPto-dependent Pto-interacting protein3 (Adi3) is a known suppressor of cell death, and loss of its function has been correlated with cell death induction during the tomato (Solanum lycopersicum) resistance response to its pathogen Pseudomonas syringae pv tomato. However, Adi3 downstream interactors that may play a role in cell death regulation have not been identified. We used a yeast two-hybrid screen to identify the plant SnRK1 (for Sucrose non-Fermenting-1-Related Protein Kinase1) protein as an Adi3-interacting protein. SnRK1 functions as a regulator of carbon metabolism and responses to biotic and abiotic stresses. SnRK1 exists in a heterotrimeric complex with a catalytic α-subunit (SnRK1), a substrate-interacting β-subunit, and a regulatory γ-subunit. Here, we show that Adi3 interacts with, but does not phosphorylate, the SnRK1 α-subunit. The ability of Adi3 to phosphorylate the four identified tomato β-subunits was also examined, and it was found that only the Galactose Metabolism83 (Gal83) β-subunit was phosphorylated by Adi3. This phosphorylation site on Gal83 was identified as serine-26 using a mutational approach and mass spectrometry. In vivo expression of Gal83 indicates that it contains multiple phosphorylation sites, one of which is serine-26. An active SnRK1 complex containing Gal83 as the β-subunit and sucrose nonfermenting4 as the γ-subunit was constructed to examine functional aspects of the Adi3 interaction with SnRK1 and Gal83. These assays revealed that Adi3 is capable of suppressing the kinase activity of the SnRK1 complex through Gal83 phosphorylation plus the interaction with SnRK1 and suggested that this function may be related to the cell death suppression activity of Adi3.
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http://dx.doi.org/10.1104/pp.112.198432 | DOI Listing |
Future Oncol
September 2025
Department of General Surgery, Institute of General Surgery, Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou University, Yangzhou, China.
Immune checkpoint therapy has demonstrated significant potential in the treatment of various solid tumors. Among these, tumor-induced immunosuppression mediated by programmed cell death protein 1 (PD-1) represents a critical checkpoint. PD-1/programmed death-ligand 1 (PD-L1) inhibitors have been proven to exhibit substantial efficacy in solid tumors such as melanoma and bladder cancer.
View Article and Find Full Text PDFAppl Immunohistochem Mol Morphol
September 2025
Department of Pathology, Yantai Yuhuangding Hospital of Qingdao University, Yantai, P. R. China.
To investigate the clinicopathological characteristics of non-HPV-related common differentiated penile squamous cell carcinoma, and to observe and analyze the changes of TP53 gene and the expression and significance of TP53, P16, programmed death-ligand 1 (PD-L1), epidermal growth factor receptor (EGFR), androgen receptor (AR), human epidermal growth factor receptor-2 (HER2), and Ki67 proteins in tumor tissue. A total of 65 patients with penile squamous cell carcinoma diagnosed from May 2008 to May 2020 in Yantai Yuhuangding Hospital were retrospectively analyzed, and tumors were confirmed as non-HPV-associated common differentiated squamous cell carcinoma of the penis with negative HPV molecular tests in 55 patients. The relevant clinicopathological data of 55 patients were collected, and the TP53 gene mutation was detected by applying first-generation sequencing technology.
View Article and Find Full Text PDFArch Pharm (Weinheim)
September 2025
Chemistry Department, Faculty of Science, Ain Shams University, Cairo, Egypt.
Through applying the hybridization technique, new coumarin derivatives (2-17) were prepared with substitution at coumarin C-3 utilizing various heterocyclic derivatives, aiming to afford multi-target carbonic anhydrases (CAs) IX/XII and topoisomerase II (Topo II) inhibitors with potent antiproliferative activity. Eight different cell lines were used to evaluate the growth inhibition percentages (GI%) of cancer cells determined by coumarin analogues 1-17. Analogues 16 and 17 had the most substantial cytotoxic effects, achieving mean GI% of 86.
View Article and Find Full Text PDFMol Ther
September 2025
Center for Single-Cell Omics, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China; State Key Laboratory of Systems Medicine for Cancer, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Pancreatic Cancer Heterogeneity, Candiolo Cancer Institute
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with poor prognosis, partly due to cancer stem cells (CSCs) that drive progression and treatment resistance. We explored the therapeutic potential of inducing cuproptosis, a copper-dependent regulated cell death, in CSC-enriched PDAC models. Using human and murine PDAC models, we evaluated elesclomol, a copper transport enhancer.
View Article and Find Full Text PDFJ Toxicol Environ Health A
September 2025
Department of Sciences, University of Franca, Franca, São Paulo, Brazil.
Pediatric high-grade gliomas remain a significant therapeutic challenge due to their resistance to conventional treatments. The aim of this study was to investigate the cytotoxic potential of solamargine (SM), a natural glycoalkaloid, alone and in combination with the chemotherapeutic agent temozolomide (TMZ) against the human KNS-42 glioma cell line. Solamargine significantly reduced cell viability and proliferation in a concentration-, time-, and hypoxia-dependent manner, while selectively sparing non-tumor human astrocytes (NHA).
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