Brechmann, Markus, Mock, Thomas, Nickles, Dorothee, Kiessling, Michael, Weit, Nicole, Breuer, Rebecca, Mueller, Wolfgang, Wabnitz, Guido ORCID: 0000-0001-5101-9885, Frey, Felice, Nicolay, Jan P., Booken, Nina, Samstag, Yvonne, Klemke, Claus-Detlev, Herling, Marco, Boutros, Michael ORCID: 0000-0002-9458-817X, Krammer, Peter H. and Arnold, Ruediger (2012). A PP4 Holoenzyme Balances Physiological and Oncogenic Nuclear Factor-Kappa B Signaling in T Lymphocytes. Immunity, 37 (4). S. 697 - 709. CAMBRIDGE: CELL PRESS. ISSN 1074-7613

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Abstract

Signal transduction to nuclear factor-kappa B (NE-kappa B) 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-kappa B activity in T lymphocytes. PP4R1 formed part of a distinct PP4 holoenzyme and bridged the inhibitor of NF-kappa B 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-kappa B signaling in NF-kappa B-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 NE-kappa B signaling in a subgroup of T cell lymphomas.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Brechmann, MarkusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mock, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nickles, DorotheeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kiessling, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Weit, NicoleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Breuer, RebeccaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mueller, WolfgangUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wabnitz, GuidoUNSPECIFIEDorcid.org/0000-0001-5101-9885UNSPECIFIED
Frey, FeliceUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nicolay, Jan P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Booken, NinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Samstag, YvonneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Klemke, Claus-DetlevUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Herling, MarcoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Boutros, MichaelUNSPECIFIEDorcid.org/0000-0002-9458-817XUNSPECIFIED
Krammer, Peter H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Arnold, RuedigerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-480925
DOI: 10.1016/j.immuni.2012.07.014
Journal or Publication Title: Immunity
Volume: 37
Number: 4
Page Range: S. 697 - 709
Date: 2012
Publisher: CELL PRESS
Place of Publication: CAMBRIDGE
ISSN: 1074-7613
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
INDUCED CELL-DEATH; ANTIGEN RECEPTORS; PHOSPHATASE 4; ACTIVATION; LYMPHOMA; COMPLEX; SUPPRESSION; PATHWAY; RECRUITMENT; SENSITIVITYMultiple languages
ImmunologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/48092

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