CIP2A Promotes T-Cell Activation and Immune Response to Listeria monocytogenes Infection

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http://hdl.handle.net/10138/163092

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Come , C , Cvrljevic , A , Khan , M M , Treise , I , Adler , T , Aguilar-Pimentel , J A , Au-Yeung , B , Sittig , E , Laajala , T D , Chen , Y , Oeder , S , Calzada-Wack , J , Horsch , M , Aittokallio , T , Busch , D H , Ollert , M W , Neff , F , Beckers , J , Gailus-Durner , V , Fuchs , H , de Angelis , M H , Chen , Z , Lahesmaa , R & Westermarck , J 2016 , ' CIP2A Promotes T-Cell Activation and Immune Response to Listeria monocytogenes Infection ' PLoS One , vol. 11 , no. 4 , 0152996 . DOI: 10.1371/journal.pone.0152996

Title: CIP2A Promotes T-Cell Activation and Immune Response to Listeria monocytogenes Infection
Author: Come, Christophe; Cvrljevic, Anna; Khan, Mohd Moin; Treise, Irina; Adler, Thure; Aguilar-Pimentel, Juan Antonio; Au-Yeung, Byron; Sittig, Eleonora; Laajala, Teemu Daniel; Chen, Yiling; Oeder, Sebastian; Calzada-Wack, Julia; Horsch, Marion; Aittokallio, Tero; Busch, Dirk H.; Ollert, Markus W.; Neff, Frauke; Beckers, Johannes; Gailus-Durner, Valerie; Fuchs, Helmut; de Angelis, Martin Hrabe; Chen, Zhi; Lahesmaa, Riitta; Westermarck, Jukka
Contributor: University of Helsinki, Institute for Molecular Medicine Finland
Date: 2016-04-21
Language: eng
Number of pages: 18
Belongs to series: PLoS One
ISSN: 1932-6203
URI: http://hdl.handle.net/10138/163092
Abstract: The oncoprotein Cancerous Inhibitor of Protein Phosphatase 2A ( CIP2A) is overexpressed in most malignancies and is an obvious candidate target protein for future cancer therapies. However, the physiological importance of CIP2A-mediated PP2A inhibition is largely unknown. As PP2A regulates immune responses, we investigated the role of CIP2A in normal immune system development and during immune response in vivo. We show that CIP2A-deficient mice (CIP2A(HOZ)) present a normal immune system development and function in unchallenged conditions. However when challenged with Listeria monocytogenes, CIP2A(HOZ) mice display an impaired adaptive immune response that is combined with decreased frequency of both CD4(+) T-cells and CD8(+) effector T-cells. Importantly, the cell autonomous effect of CIP2A deficiency for T-cell activation was confirmed. Induction of CIP2A expression during T-cell activation was dependent on Zap70 activity. Thus, we reveal CIP2A as a hitherto unrecognized mediator of T-cell activation during adaptive immune response. These results also reveal CIP2A(HOZ) as a possible novel mouse model for studying the role of PP2A activity in immune regulation. On the other hand, the results also indicate that CIP2A targeting cancer therapies would not cause serious immunological side-effects.
Subject: PROTEIN PHOSPHATASE 2A
CATALYTIC-ACTIVITY
CANCER
APOPTOSIS
PP2A
ONCOPROTEIN
EXPRESSION
INHIBITOR
KINASE
ZAP70
3111 Biomedicine
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