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A PP4 holoenzyme balances physiological and oncogenic nuclear factor-kappa B signaling in T lymphocytes

Summary: Signal transduction to nuclear factor-kappa B (NF-κB) involves multiple kinases and phosphorylated target proteins, but little is known about signal termination by dephosphorylation. By RNAi screening, we have identified protein phosphatase 4 regulatory subunit 1 (PP4R1) as a negative regul...

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Bibliographische Detailangaben
Hauptverfasser: Brechmann, Markus (VerfasserIn) , Wabnitz, Guido H. (VerfasserIn) , Nicolay, Jan Peter (VerfasserIn) , Booken, Nina (VerfasserIn) , Samstag, Yvonne (VerfasserIn) , Klemke, Claus-Detlev (VerfasserIn) , Boutros, Michael (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 2012
In: Immunity
Year: 2012, Jahrgang: 37, Heft: 4, Pages: 697-708
ISSN:1097-4180
DOI:10.1016/j.immuni.2012.07.014
Online-Zugang:Verlag, kostenfrei, Volltext: http://dx.doi.org/10.1016/j.immuni.2012.07.014
Verlag, kostenfrei, Volltext: http://www.sciencedirect.com/science/article/pii/S1074761312004268
Volltext
Verfasserangaben:Markus Brechmann, Thomas Mock, Dorothee Nickles, Michael Kiessling, Nicole Weit, Rebecca Breuer, Wolfgang Müller, Guido Wabnitz, Felice Frey, Jan P. Nicolay, Nina Booken, Yvonne Samstag, Claus-Detlev Klemke, Marco Herling, Michael Boutros, Peter H. Krammer, and Rüdiger Arnold
Beschreibung
Zusammenfassung:Summary: Signal transduction to nuclear factor-kappa B (NF-κB) involves multiple kinases and phosphorylated target proteins, but little is known about signal termination by dephosphorylation. By RNAi screening, we have identified protein phosphatase 4 regulatory subunit 1 (PP4R1) as a negative regulator of NF-κB activity in T lymphocytes. PP4R1 formed part of a distinct PP4 holoenzyme and bridged the inhibitor of NF-κB kinase (IKK) complex and the phosphatase PP4c, thereby directing PP4c activity to dephosphorylate and inactivate the IKK complex. PP4R1 expression was triggered upon activation and proliferation of primary human T lymphocytes and deficiency for PP4R1 caused sustained and increased IKK activity, T cell hyperactivation, and aberrant NF-κB signaling in NF-κB-addicted T cell lymphomas. Collectively, our results unravel PP4R1 as a previously unknown activation-associated negative regulator of IKK activity in lymphocytes whose downregulation promotes oncogenic NF-κB signaling in a subgroup of T cell lymphomas.
Beschreibung:Published online: October 18, 2012
Gesehen am 25.06.2018
Beschreibung:Online Resource
ISSN:1097-4180
DOI:10.1016/j.immuni.2012.07.014

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