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

• Verfasst von: Brechmann, Markus [VerfasserIn]
• Verfasst von: Wabnitz, Guido H. [VerfasserIn]
• Verfasst von: Nicolay, Jan Peter [VerfasserIn]
• Verfasst von: Booken, Nina [VerfasserIn]
• Verfasst von: Samstag, Yvonne [VerfasserIn]
• Verfasst von: Klemke, Claus-Detlev [VerfasserIn]
• Verfasst von: Boutros, Michael [VerfasserIn]
• Titel: A PP4 holoenzyme balances physiological and oncogenic nuclear factor-kappa B signaling in T lymphocytes
• Verf.angabe: 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
• Jahr: 2012
• Umfang: 12 S.
• Fussnoten: Published online: October 18, 2012 ; Gesehen am 25.06.2018
• Titel Quelle: Enthalten in: Immunity
• Ort Quelle: [Cambridge, Mass.] : Cell Press, 1994
• Jahr Quelle: 2012
• Band/Heft Quelle: 37(2012), 4, Seite 697-708
• ISSN Quelle: 1097-4180
• DOI: doi:10.1016/j.immuni.2012.07.014
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1576801780

Abstract

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.