Formation of the Alarmones Diadenosine Triphosphate and Tetraphosphate by Ubiquitin- and Ubiquitin-like-Activating Enzymes.
Diadenosine polyphosphates (ApnAs) 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 ApnAs are alarmones triggering stress-adaptive processes. The major synthesis pathway of ApnAs 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 ApnA 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 ApnA formation for the first time.
['Götz|Kathrin H|KH|', 'Mex|Martin|M|', 'Stuber|Katrin|K|', 'Offensperger|Fabian|F|', 'Scheffner|Martin|M|', 'Marx|Andreas|A|']
D055162:Biocatalysis D002851:Chromatography, High Pressure Liquid D015226:Dinucleoside Phosphates D006801:Humans D013058:Mass Spectrometry D016296:Mutagenesis D011994:Recombinant Proteins D025841:Small Ubiquitin-Related Modifier Proteins D025801:Ubiquitin D044764:Ubiquitin-Activating Enzymes
alarmone diadenosine triphosphate ApnA ubiquitin-like proteins ATP UBA1 diadenosine tetraphosphate ubiquitin-activating enzyme