Tollip is a mediator of protein sumoylation

• Published in: PloS one 2009-02, Vol.4 (2), p.e4404-e4404
• Main Authors: Ciarrocchi, Alessia, D'Angelo, Romina, Cordiglieri, Chiara, Rispoli, Ada, Santi, Spartaco, Riccio, Massimo, Carone, Simona, Mancia, Anna Laura, Paci, Simone, Cipollini, Elena, Ambrosetti, Davide, Melli, Marialuisa
• Format: Article
• Language: English
• Subjects: Animals; Arsenic; Biochemistry/Chemical Biology of the Cell; Biology; Cell Biology; Cloning; Daxx protein; Enzymes; Fluorescent Antibody Technique; HeLa Cells; Humans; Immunoprecipitation; Interleukin 1; Interleukin 1 receptors; Interleukins; Intracellular Signaling Peptides and Proteins - genetics; Intracellular Signaling Peptides and Proteins - metabolism; Kinases; Laboratories; Localization; Molecular Biology; Protein transport; Proteins; Rats; Rats, Sprague-Dawley; Receptors, Interleukin-1 - metabolism; Recombinants; SUMO protein; SUMO-1 Protein - metabolism; Traffic; Transcription; Transcription factors; Translocation; Trends; Two-Hybrid System Techniques; Ubiquitin; Yeast
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0004404

Tollip is an interactor of the interleukin-1 receptor involved in its activation. The endosomal turnover of ubiquitylated IL-1RI is also controlled by Tollip. Furthermore, together with Tom1, Tollip has a general role in endosomal protein traffic. This work shows that Tollip is involved in the sumoylation process. Using the yeast two-hybrid technique, we have isolated new Tollip partners including two sumoylation enzymes, SUMO-1 and the transcriptional repressor Daxx. The interactions were confirmed by GST-pull down experiments and immunoprecipitation of the co-expressed recombinants. More specifically, we show that the TIR domain of the cytoplasmic region of IL-1RI is a sumoylation target of Tollip. The sumoylated and unsumoylated RanGAP-1 protein also interacts with Tollip, suggesting a possible role in RanGAP-1 modification and nuclear-cytoplasmic protein translocation. In fact, Tollip is found in the nuclear bodies of SAOS-2/IL-1RI cells where it colocalizes with SUMO-1 and the Daxx repressor. We conclude that Tollip is involved in the control of both nuclear and cytoplasmic protein traffic, through two different and often contrasting processes: ubiquitylation and sumoylation.