Ubiquitination of the common cytokine receptor gammac and regulation of expression by an ubiquitination/deubiquitination machinery.
The common cytokine receptor gamma(c) is shared by the interleukin-2, -4, -7, -9, -15, and -21 receptors, and is essential for lymphocyte proliferation and survival. The regulation of gamma(c) receptor expression level is therefore critical for the ability of cells to respond to these cytokines. We previously reported that gamma(c) is efficiently constitutively internalized and addressed towards a degradation endocytic compartment. We show that gamma(c) is ubiquitinated and also associated to ubiquitinated proteins. We report that the ubiquitin-ligase c-Cbl induces gamma(c) down-regulation. In addition, the ubiquitin-hydrolase, DUB-2, counteracts the effect of c-Cbl on gamma(c) expression. We show that an increase in DUB-2 expression correlates with an increased gamma(c) half-life, resulting in the up-regulation of the receptor. Altogether, we show that gamma(c) is the target of an ubiquitination mechanism and its expression level can be regulated through the activities of a couple of ubiquitin-ligase/ubiquitin-hydrolase enzymes, namely c-Cbl/DUB-2.
Gesbert
Franck
F
Unité de Biologie des Interactions Cellulaires, Institut Pasteur, CNRS URA 2582, 25-28 rue du Dr. Roux, 75724 Paris Cedex 15, France.
Malardé
Valérie
V
Dautry-Varsat
Alice
A
D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D005786:Gene Expression Regulation / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D053631:Interleukin Receptor Common gamma Subunit; D020395:Receptors, Interleukin-7 / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism*
C507941:IL2RG protein, human; D053631:Interleukin Receptor Common gamma Subunit; D020395:Receptors, Interleukin-7; D025801:Ubiquitin