Tollip is a mediator of protein sumoylation.
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.
Ciarrocchi
Alessia
A
Department of Biology, Bologna University, Bologna, Italy.
D'Angelo
Romina
R
Cordiglieri
Chiara
C
Rispoli
Ada
A
Santi
Spartaco
S
Riccio
Massimo
M
Carone
Simona
S
Mancia
Anna Laura
AL
Paci
Simone
S
Cipollini
Elena
E
Ambrosetti
Davide
D
Melli
Marialuisa
M
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
D047908:Intracellular Signaling Peptides and Proteins; D017472:Receptors, Interleukin-1; D025842:SUMO-1 Protein; C539480:tollip protein, rat