Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Hamerman, J.A. et al.

Hamerman, Hayashi, Schroeder, Gygi, Haas, Hampson, Coughlin, Aebersold, Aderem,

Serpin 2a is induced in activated macrophages and conjugates to a ubiquitin homolog.

After i.p. infection of mice with the intracellular bacterium Mycobacterium bovis bacillus Calmette-GuÃ©rin, macrophages recovered from the peritoneal cavity display classical signs of immune activation. We have identified a member of the serine protease inhibitor (serpin) family which is highly induced in macrophages during bacillus Calmette-GuÃ©rin infection. Serpin 2a (spi2a) expression is also induced in macrophages in vivo during infection with Salmonella typhimurium and Listeria monocytogenes, and in vitro by a variety of bacteria and bacterial products. The cytokine IFN-gamma also induces spi2a expression in macrophages, and this induction is synergistic with bacterial products. We also demonstrate here that a ubiquitin homolog, IFN-stimulated gene of 15-kDa (ISG15), is strongly induced during in vitro and in vivo activation of macrophages and that it conjugates to spi2a in activated macrophages. The ISG15-spi2a conjugates were identified by tandem mass spectrometry and contained spi2a conjugated to either one or two molecules of ISG15. Whereas spi2a was induced by either bacterial products or IFN-gamma, ISG15 was induced only by bacterial products. Although many protein targets have been described for ubiquitin conjugation, spi2a is the first ISG15-modified protein to be reported. Macrophage activation is accompanied by the activation of a variety of proteases. It is of interest that a member of the serine protease inhibitor family is concomitantly induced and modified by a ubiquitin-like protein.[1]

References

Serpin 2a is induced in activated macrophages and conjugates to a ubiquitin homolog. Hamerman, J.A., Hayashi, F., Schroeder, L.A., Gygi, S.P., Haas, A.L., Hampson, L., Coughlin, P., Aebersold, R., Aderem, A. J. Immunol. (2002) [Pubmed]

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