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Formation of the Alarmones Diadenosine Triphosphate and Tetraphosphate by Ubiquitin- and Ubiquitin-like-Activating Enzymes

Formation of the Alarmones Diadenosine Triphosphate and Tetraphosphate by Ubiquitin- and Ubiquitin-like-Activating Enzymes

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GÖTZ, Kathrin H., Martin MEX, Katrin STUBER, Fabian OFFENSPERGER, Martin SCHEFFNER, Andreas MARX, 2019. Formation of the Alarmones Diadenosine Triphosphate and Tetraphosphate by Ubiquitin- and Ubiquitin-like-Activating Enzymes. In: Cell Chemical Biology. 26(11), pp. 1535-1543.e5. eISSN 2451-9456. Available under: doi: 10.1016/j.chembiol.2019.08.004

@article{Gotz2019-11Forma-47032, title={Formation of the Alarmones Diadenosine Triphosphate and Tetraphosphate by Ubiquitin- and Ubiquitin-like-Activating Enzymes}, year={2019}, doi={10.1016/j.chembiol.2019.08.004}, number={11}, volume={26}, journal={Cell Chemical Biology}, pages={1535--1543.e5}, author={Götz, Kathrin H. and Mex, Martin and Stuber, Katrin and Offensperger, Fabian and Scheffner, Martin and Marx, Andreas} }

Stuber, Katrin eng Götz, Kathrin H. Scheffner, Martin Diadenosine polyphosphates (Ap <sub>n</sub>As) such as diadenosine tri- and tetraphosphates are formed in prokaryotic as well as eukaryotic cells. Since upon stress intracellular ApnA concentrations increase, it was postulated that Ap <sub>n</sub>As are alarmones triggering stress-adaptive processes. The major synthesis pathway of Ap <sub>n</sub>As is assumed to be a side reaction of amino acid activation. How this process is linked to stress adaptation remains enigmatic. The first step of one of the most prominent eukaryotic post-translational modification systems-the conjugation of ubiquitin (Ub) and ubiquitin-like proteins (Ubl) to target proteins-involves the formation of an adenylate as intermediate. Like Ap <sub>n</sub>A formation, Ub and Ubl conjugation is significantly enhanced during stress conditions. Here, we demonstrate that diadenosine tri- and tetraphosphates are indeed synthesized during activation of Ub and Ubls. This links one of the most prevalent eukaryotic protein-modification systems to Ap <sub>n</sub>A formation for the first time. 2019-09-25T13:41:22Z Offensperger, Fabian 2019-11 Scheffner, Martin 2019-09-25T13:41:22Z Mex, Martin Stuber, Katrin Marx, Andreas Marx, Andreas Offensperger, Fabian Götz, Kathrin H. Formation of the Alarmones Diadenosine Triphosphate and Tetraphosphate by Ubiquitin- and Ubiquitin-like-Activating Enzymes Mex, Martin

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