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The expression of GBP\u20101 is inducible by inflammatory cytokines, and the protein is involved in inflammatory processes and host defence against cellular pathogens. GBP\u20101 is the first GTPase which was described to be secreted by eukaryotic cells. Here, we report that precipitation of GBP\u20101 with GMP\u2010agarose from cell culture supernatants co\u2010purified a 47\u2010kD fragment of GBP\u20101 (p47\u2010GBP\u20101) in addition to the 67\u2010kD full\u2010length form. MALDI\u2010TOF sequencing revealed that p47\u2010GBP\u20101 corresponds to the C\u2010terminal helical part of GBP\u20101 and lacks most of the globular GTPase domain. <jats:italic>In silico<\/jats:italic> analyses of protease target sites, together with cleavage experiments <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic>, showed that p67\u2010GBP\u20101 is cleaved by the inflammatory caspases 1 and 5, leading to the formation of p47\u2010GBP\u20101. Furthermore, the secretion of p47\u2010GBP\u20101 was found to occur <jats:italic>via<\/jats:italic> a non\u2010classical secretion pathway and to be dependent on caspase\u20101 activity but independent of inflammasome activation. Finally, we showed that p47\u2010GBP\u20101 represents the predominant form of secreted GBP\u20101, both in cell culture supernatants and, <jats:italic>in vivo,<\/jats:italic> in the cerebrospinal fluid of patients with bacterial meningitis, indicating that it may represent the biologically active form of extracellular GBP\u20101. These findings confirm the involvement of caspase\u20101 in non\u2010classical secretion mechanisms and open novel perspectives for the extracellular function of secreted GBP\u20101.<\/jats:p>","DOI":"10.1111\/jcmm.13116","type":"journal-article","created":{"date-parts":[[2017,3,8]],"date-time":"2017-03-08T10:42:45Z","timestamp":1488969765000},"page":"1954-1966","source":"Crossref","is-referenced-by-count":18,"title":["Processing and secretion of guanylate binding protein\u20101 depend on inflammatory caspase activity"],"prefix":"10.1111","volume":"21","author":[{"given":"Elisabeth","family":"Naschberger","sequence":"first","affiliation":[{"name":"Division of Molecular and Experimental Surgery Department of Surgery Friedrich\u2010Alexander\u2010Universit\u00e4t (FAU) Erlangen\u2010N\u00fcrnberg and Universit\u00e4tsklinikum Erlangen Translational Research Center Erlangen 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