Ubiquitination of the common cytokine receptor gammac and regulation of expression by an ubiquitination/deubiquitination machinery. - Institut Pasteur Access content directly
Journal Articles Biochemical and Biophysical Research Communications Year : 2005

Ubiquitination of the common cytokine receptor gammac and regulation of expression by an ubiquitination/deubiquitination machinery.

Abstract

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.

Dates and versions

pasteur-00166609 , version 1 (07-08-2007)

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Franck Gesbert, Valérie Malardé, Alice Dautry-Varsat. Ubiquitination of the common cytokine receptor gammac and regulation of expression by an ubiquitination/deubiquitination machinery.. Biochemical and Biophysical Research Communications, 2005, 334 (2), pp.474-80. ⟨10.1016/j.bbrc.2005.06.121⟩. ⟨pasteur-00166609⟩

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