Omanische Heilpflanze im Fokus der Phytochemie IPB-Wissenschaftler und Partner aus Dhofar haben jüngst die omanische Heilpflanze Terminalia dhofarica unter die phytochemische Lupe genommen. Die Pflanze ist reich an…
Geschmack ist vorhersagbar: Mit FlavorMiner. FlavorMiner heißt das Tool, das IPB-Chemiker und Partner aus Kolumbien jüngst entwickelt haben. Das Programm kann, basierend auf maschinellem Lernen (KI), anhand der…
UFMylation involves the covalent modification of substrate proteins with UFM1 (Ubiquitin-fold modifier 1) and is important for maintaining ER homeostasis. Stalled translation triggers the UFMylation of ER-bound ribosomes and activates C53-mediated autophagy to clear toxic polypeptides. C53 contains noncanonical shuffled ATG8-interacting motifs (sAIMs) that are essential for ATG8 interaction and autophagy initiation. However, the mechanistic basis of sAIM-mediated ATG8 interaction remains unknown. Here, we show that C53 and sAIMs are conserved across eukaryotes but secondarily lost in fungi and various algal lineages. Biochemical assays showed that the unicellular alga Chlamydomonas reinhardtii has a functional UFMylation pathway, refuting the assumption that UFMylation is linked to multicellularity. Comparative structural analyses revealed that both UFM1 and ATG8 bind sAIMs in C53, but in a distinct way. Conversion of sAIMs into canonical AIMs impaired binding of C53 to UFM1, while strengthening ATG8 binding. Increased ATG8 binding led to the autoactivation of the C53 pathway and sensitization of Arabidopsis thaliana to ER stress. Altogether, our findings reveal an ancestral role of sAIMs in UFMylation-dependent fine-tuning of C53-mediated autophagy activation.
Publikation
Ai, H.; Bellstaedt, J.; Bartusch, K. S.; Eschen‐Lippold, L.; Babben, S.; Balcke, G. U.; Tissier, A.; Hause, B.; Andersen, T. G.; Delker, C.; Quint, M.;Auxin‐dependent regulation of cell division rates governs root thermomorphogenesisEMBO J.42e111926(2023)DOI: 10.15252/embj.2022111926
Roots are highly plastic organs enabling plants to adapt to a changing below-ground environment. In addition to abiotic factors like nutrients or mechanical resistance, plant roots also respond to temperature variation. Below the heat stress threshold, Arabidopsis thaliana seedlings react to elevated temperature by promoting primary root growth, possibly to reach deeper soil regions with potentially better water saturation. While above-ground thermomorphogenesis is enabled by thermo-sensitive cell elongation, it was unknown how temperature modulates root growth. We here show that roots are able to sense and respond to elevated temperature independently of shoot-derived signals. This response is mediated by a yet unknown root thermosensor that employs auxin as a messenger to relay temperature signals to the cell cycle. Growth promotion is achieved primarily by increasing cell division rates in the root apical meristem, depending on de novo local auxin biosynthesis and temperature-sensitive organization of the polar auxin transport system. Hence, the primary cellular target of elevated ambient temperature differs fundamentally between root and shoot tissues, while the messenger auxin remains the same.
Publikation
Drača, D.; Edeler, D.; Saoud, M.; Dojčinović, B.; Dunđerović, D.; Đmura, G.; Maksimović-Ivanić, D.; Mijatović, S.; Kaluđerović, G. N.;Antitumor potential of cisplatin loaded into SBA-15 mesoporous silica nanoparticles against B16F1 melanoma cells: in vitro and in vivo studiesJ. Inorg. Biochem.217111383(2021)DOI: 10.1016/j.jinorgbio.2021.111383
CP (cisplatin) and mesoporous silica SBA-15 (Santa Barbara amorphous 15) loaded with CP (→SBA-15|CP) were tested in vitro and in vivo against low metastatic mouse melanoma B16F1 cell line. SBA-15 only, as drug carrier, is found to be not active, while CP and SBA-15|CP revealed high cytotoxicity in lower μM range. The activity of SBA-15|CP was found similar to the activity of CP alone. Both CP and SBA-15|CP induced inhibition of cell proliferation (carboxyfluorescein succinimidyl ester - CFSE assay) along with G2/M arrest (4′,6-diamidino-2-phenylindole - DAPI assay). Apoptosis (Annexin V/ propidium iodide - PI assay), through caspase activation (apostat assay) and nitric oxide (NO) production (diacetate(4-amino-5-methylamino-2′,7′-difluorofluorescein-diacetat) - DAF FM assay), was identified as main mode of cell death. However, slight elevated autophagy (acridine orange - AO assay) was detected in treated B16F1 cells. CP and SBA-15|CP did not affect production of ROS (reactive oxygen species) in B16F1 cells. Both SBA-15|CP and CP induced in B16F1 G2 arrest and subsequent senescence. SBA-15|CP, but not CP, blocked the growth of melanoma in C57BL/6 mice. Moreover, hepato- and nephrotoxicity in SBA-15|CP treated animals were diminished in comparison to CP confirming multiply improved antitumor potential of immobilized CP. Outstandingly, SBA-15 boosted in vivo activity and diminished side effects of CP.
Publikation
Pantelić, N. ?.; Zmejkovski, B. B.; Božić, B.; Dojčinović, B.; Banjac, N. R.; Wessjohann, L. A.; Kaluđerović, G. N.;Synthesis, characterization and in vitro biological evaluation of novel organotin(IV) compounds with derivatives of 2-(5-arylidene-2,4-dioxothiazolidin-3-yl)propanoic acidJ. Inorg. Biochem.211111207(2020)DOI: 10.1016/j.jinorgbio.2020.111207
Two novel triphenyltin(IV) compounds, [Ph3SnL1] (L1 = 2-(5-(4-fluorobenzylidene)-2,4-dioxotetrahydrothiazole-3-yl)propanoate (1)) and [Ph3SnL2] (L2 = 2-(5-(5-methyl-2-furfurylidene)-2,4-dioxotetrahydrothiazole-3-yl)propanoate (2)) were synthesized and characterized by FT-IR, (1H and 13C) NMR spectroscopy, mass spectrometry, and elemental microanalysis. The in vitro anticancer activity of the synthesized organotin(IV) compounds was determined against four tumor cell lines: PC-3 (prostate), HT-29 (colon), MCF-7 (breast), and HepG2 (hepatic) using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-12 diphenyltetrazolium bromide) and CV (crystal violet) assays. The IC50 values are found to be in the range from 0.11 to 0.50 μM. Compound 1 exhibits the highest activity toward PC-3 cells (IC50 = 0.115 ± 0.009 μM; CV assay). The tin and platinum uptake in PC-3 cells showed a threefold lower uptake of tin in comparison to platinum (as cisplatin). Together with its higher activity this indicates a much higher cell inhibition potential of the tin compounds (calculated to ca. 50 to 100 times). Morphological analysis suggested that the compounds induce apoptosis in PC-3 cells, and flow cytometry analysis revealed that 1 and 2 induce autophagy as well as NO (nitric oxide) production.