title: Tollip is a mediator of protein sumoylation.
abstract: 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.
authors.affiliation: Department of Biology, Bologna University, Bologna, Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Ciarrocchi
authors.forename: Romina
authors.initials: R
authors.lastname: D'Angelo
authors.forename: Chiara
authors.initials: C
authors.lastname: Cordiglieri
authors.forename: Ada
authors.initials: A
authors.lastname: Rispoli
authors.forename: Spartaco
authors.initials: S
authors.lastname: Santi
authors.forename: Massimo
authors.initials: M
authors.lastname: Riccio
authors.forename: Simona
authors.initials: S
authors.lastname: Carone
authors.forename: Anna Laura
authors.initials: AL
authors.lastname: Mancia
authors.forename: Simone
authors.initials: S
authors.lastname: Paci
authors.forename: Elena
authors.initials: E
authors.lastname: Cipollini
authors.forename: Davide
authors.initials: D
authors.lastname: Ambrosetti
authors.forename: Marialuisa
authors.initials: M
authors.lastname: Melli
mesh_terms: D000818:Animals; D005455:Fluorescent Antibody Technique; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017472:Receptors, Interleukin-1 / Q000378:metabolism; D025842:SUMO-1 Protein / Q000378:metabolism*; D020798:Two-Hybrid System Techniques
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D017472:Receptors, Interleukin-1; D025842:SUMO-1 Protein; C539480:tollip protein, rat