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RNF41 (Nrdp1) controls type 1 cytokine receptor degradation and ectodomain shedding

Cytokines, such as interferons, erythropoietin, leptin and most interleukins, signal through type 1 cytokine receptors and activate the canonical JAK–STAT pathway. Aberrant cytokine signalling underlies numerous pathologies and adequate, temporary receptor activation is therefore under tight control...

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Autores principales: Wauman, Joris, De Ceuninck, Leentje, Vanderroost, Nele, Lievens, Sam, Tavernier, Jan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Company of Biologists 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3115735/
https://www.ncbi.nlm.nih.gov/pubmed/21378310
http://dx.doi.org/10.1242/jcs.078055
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author Wauman, Joris
De Ceuninck, Leentje
Vanderroost, Nele
Lievens, Sam
Tavernier, Jan
author_facet Wauman, Joris
De Ceuninck, Leentje
Vanderroost, Nele
Lievens, Sam
Tavernier, Jan
author_sort Wauman, Joris
collection PubMed
description Cytokines, such as interferons, erythropoietin, leptin and most interleukins, signal through type 1 cytokine receptors and activate the canonical JAK–STAT pathway. Aberrant cytokine signalling underlies numerous pathologies and adequate, temporary receptor activation is therefore under tight control. Negative-feedback mechanisms are very well studied, but cellular sensitivity also depends on the number of receptors exposed at the cell surface. This is determined by the equilibrium between receptor synthesis and transport to the plasma membrane, internalisation and recycling, degradation and ectodomain shedding, but the molecular basis of how cells establish steady state receptor levels is poorly understood. Here, we report that ring finger protein 41 (RNF41, also known as E3 ubiquitin-protein ligase Nrdp1) interacts with JAK2-associated cytokine receptor complexes and modulates their cell surface exposure and signalling. Moreover, ectopic expression of RNF41 affected turnover of leptin, leukaemia inhibitory factor and interleukin-6 receptor in a dual way: it blocked intracellular cathepsin-L-dependent receptor cleavage and concomitantly enhanced receptor shedding by metalloproteases of the ADAM family. Receptor degradation and shedding are thus interconnected phenomena with a single protein, RNF41, determining the balance.
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spelling pubmed-31157352011-06-16 RNF41 (Nrdp1) controls type 1 cytokine receptor degradation and ectodomain shedding Wauman, Joris De Ceuninck, Leentje Vanderroost, Nele Lievens, Sam Tavernier, Jan J Cell Sci Research Articles Cytokines, such as interferons, erythropoietin, leptin and most interleukins, signal through type 1 cytokine receptors and activate the canonical JAK–STAT pathway. Aberrant cytokine signalling underlies numerous pathologies and adequate, temporary receptor activation is therefore under tight control. Negative-feedback mechanisms are very well studied, but cellular sensitivity also depends on the number of receptors exposed at the cell surface. This is determined by the equilibrium between receptor synthesis and transport to the plasma membrane, internalisation and recycling, degradation and ectodomain shedding, but the molecular basis of how cells establish steady state receptor levels is poorly understood. Here, we report that ring finger protein 41 (RNF41, also known as E3 ubiquitin-protein ligase Nrdp1) interacts with JAK2-associated cytokine receptor complexes and modulates their cell surface exposure and signalling. Moreover, ectopic expression of RNF41 affected turnover of leptin, leukaemia inhibitory factor and interleukin-6 receptor in a dual way: it blocked intracellular cathepsin-L-dependent receptor cleavage and concomitantly enhanced receptor shedding by metalloproteases of the ADAM family. Receptor degradation and shedding are thus interconnected phenomena with a single protein, RNF41, determining the balance. Company of Biologists 2011-03-15 /pmc/articles/PMC3115735/ /pubmed/21378310 http://dx.doi.org/10.1242/jcs.078055 Text en © 2011. http://creativecommons.org/licenses/by-nc-sa/3.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial Share Alike License, which permits unrestricted non-commercial use, distribution and reproduction in any medium provided that the original work is properly cited and all further distributions of the work or adaptation are subject to the same Creative Commons License terms.
spellingShingle Research Articles
Wauman, Joris
De Ceuninck, Leentje
Vanderroost, Nele
Lievens, Sam
Tavernier, Jan
RNF41 (Nrdp1) controls type 1 cytokine receptor degradation and ectodomain shedding
title RNF41 (Nrdp1) controls type 1 cytokine receptor degradation and ectodomain shedding
title_full RNF41 (Nrdp1) controls type 1 cytokine receptor degradation and ectodomain shedding
title_fullStr RNF41 (Nrdp1) controls type 1 cytokine receptor degradation and ectodomain shedding
title_full_unstemmed RNF41 (Nrdp1) controls type 1 cytokine receptor degradation and ectodomain shedding
title_short RNF41 (Nrdp1) controls type 1 cytokine receptor degradation and ectodomain shedding
title_sort rnf41 (nrdp1) controls type 1 cytokine receptor degradation and ectodomain shedding
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3115735/
https://www.ncbi.nlm.nih.gov/pubmed/21378310
http://dx.doi.org/10.1242/jcs.078055
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