Fax +41 61 306 12 34 E-Mail karger@karger.ch www.karger.com Short Communication J Innate Immun 2010;2:618–624 DOI: 10.1159/000318676 Sumoylation of Drosophila Transcription Factor STAT92E Juha Grönholm   a Daniela Ungureanu   a Sari Vanhatupa   a Mika Rämet   a, b Olli Silvennoinen   a, c a  Institute of Medical Technology, University of Tampere, and b  Department of Pediatrics, and c  Center for Laboratory Medicine, Tampere University Hospital, Tampere, Finland Introduction The JAK/STAT pathway is highly conserved in the evolution from invertebrates to humans. The JAK/STAT signaling cascade is essential for several biological pro- cesses, including the control of hematopoiesis and im- mune responses, as well as for cellular homeostasis and embryonic development [1, 2]. The human JAK/STAT pathway consists of 7 STATs and 4 JAKs [3]. In Drosoph- ila melanogaster, the pathway employs only a single Janus kinase Hopscotch (Hop) and the transcription factor STAT92E as well as the receptor Domeless (Dome) [2], thus making Drosophila a useful non-redundant model to study this pathway. The activation mechanism of the JAK/STAT pathway is shared by invertebrates and humans. In Drosophila, 3 secreted ligands (Unpaired 1–3, Upd1–3) [4–6] induce the homodimerization of the Dome receptors allowing the Hop kinases to phosphorylate tyrosine residues in the re- ceptors, thus creating docking sites for the SH2 domain of STAT92E. Following the interaction with Dome, STAT92E becomes phosphorylated by Hop, leading to the homodimerization and nuclear translocation of STAT92E. In the nucleus, STAT92E binds to its target DNA sequences and acts as activator of transcription for Key Words Signal transducer and activator of transcription  STAT  Small ubiquitin-like modifier  Sumo  Sumoylation  Post-translational modification Abstract STAT92E is an essential transcription factor in Drosophila me- lanogaster for the development of several organs and the immune system. The JAK/STAT pathway employs different evolutionary conserved regulatory mechanisms to control biological processes. Numerous transcription factors in both mammals and invertebrates have been shown to be either activated or inhibited by a covalent modification with a small ubiquitin-like modifier (Sumo). Here, we show that Drosoph- ila STAT92E is modified by Sumo at a single lysine residue 187 in S2 cells. Mutation of Lys187 increases the transcriptional activity of STAT92E, thus suggesting that sumoylation of STAT92E has a repressive role in the regulation of the JAK/ STAT pathway in Drosophila melanogaster. Copyright © 2010 S. Karger AG, Basel Received: January 25, 2010 Accepted after revision: May 20, 2010 Published online: July 12, 2010 Journal of Innate Immunity Prof. Olli Silvennoinen Institute of Medical Technology University of Tampere FI–33014 Tampere (Finland) Tel. +358 3 3551 7845, Fax +358 3 3551 7332, E-Mail olli.silvennoinen  @  uta.fi © 2010 S. Karger AG, Basel 1662–811X/10/0026–0618$26.00/0 Accessible online at: www.karger.com/jin