000127357 001__ 127357 000127357 005__ 20240228140921.0 000127357 0247_ $$2doi$$a10.4049/jimmunol.1402694 000127357 0247_ $$2pmid$$apmid:25552543 000127357 0247_ $$2ISSN$$a0022-1767 000127357 0247_ $$2ISSN$$a1550-6606 000127357 0247_ $$2altmetric$$aaltmetric:3031625 000127357 037__ $$aDKFZ-2017-03382 000127357 041__ $$aeng 000127357 082__ $$a610 000127357 1001_ $$0P:(DE-He78)83227bd2ef5cb3bccf76dc974c9ad2cc$$aRattay, Kristin$$b0$$eFirst author$$udkfz 000127357 245__ $$aHomeodomain-interacting protein kinase 2, a novel autoimmune regulator interaction partner, modulates promiscuous gene expression in medullary thymic epithelial cells. 000127357 260__ $$aBethesda, Md.$$bSoc.$$c2015 000127357 3367_ $$2DRIVER$$aarticle 000127357 3367_ $$2DataCite$$aOutput Types/Journal article 000127357 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1521638687_14324 000127357 3367_ $$2BibTeX$$aARTICLE 000127357 3367_ $$2ORCID$$aJOURNAL_ARTICLE 000127357 3367_ $$00$$2EndNote$$aJournal Article 000127357 520__ $$aPromiscuous expression of a plethora of tissue-restricted Ags (TRAs) by medullary thymic epithelial cells (mTECs) plays an essential role in T cell tolerance. Although the cellular mechanisms by which promiscuous gene expression (pGE) imposes T cell tolerance have been well characterized, the underlying molecular mechanisms remain poorly understood. The autoimmune regulator (AIRE) is to date the only validated molecule known to regulate pGE. AIRE is part of higher-order multiprotein complexes, which promote transcription, elongation, and splicing of a wide range of target genes. How AIRE and its partners mediate these various effects at the molecular level is still largely unclear. Using a yeast two-hybrid screen, we searched for novel AIRE-interacting proteins and identified the homeodomain-interacting protein kinase 2 (HIPK2) as a novel partner. HIPK2 partially colocalized with AIRE in nuclear bodies upon cotransfection and in human mTECs in situ. Moreover, HIPK2 phosphorylated AIRE in vitro and suppressed the coactivator activity of AIRE in a kinase-dependent manner. To evaluate the role of Hipk2 in modulating the function of AIRE in vivo, we compared whole-genome gene signatures of purified mTEC subsets from TEC-specific Hipk2 knockout mice with control mice and identified a small set of differentially expressed genes. Unexpectedly, most differentially expressed genes were confined to the CD80(lo) mTEC subset and preferentially included AIRE-independent TRAs. Thus, although it modulates gene expression in mTECs and in addition affects the size of the medullary compartment, TEC-specific HIPK2 deletion only mildly affects AIRE-directed pGE in vivo. 000127357 536__ $$0G:(DE-HGF)POF3-314$$a314 - Tumor immunology (POF3-314)$$cPOF3-314$$fPOF III$$x0 000127357 588__ $$aDataset connected to CrossRef, PubMed, 000127357 650_7 $$2NLM Chemicals$$aAPECED protein 000127357 650_7 $$2NLM Chemicals$$aAntigens 000127357 650_7 $$2NLM Chemicals$$aCarrier Proteins 000127357 650_7 $$2NLM Chemicals$$aTranscription Factors 000127357 650_7 $$0EC 2.7.1.-$$2NLM Chemicals$$aHIPK2 protein, human 000127357 650_7 $$0EC 2.7.1.-$$2NLM Chemicals$$aHipk2 protein, mouse 000127357 650_7 $$0EC 2.7.11.1$$2NLM Chemicals$$aProtein-Serine-Threonine Kinases 000127357 7001_ $$0P:(DE-HGF)0$$aClaude, Janine$$b1 000127357 7001_ $$0P:(DE-He78)8fc65269d45cda1a54ba654f7c0cf8ec$$aRezavandy, Esmail$$b2$$udkfz 000127357 7001_ $$0P:(DE-He78)ce86d7d02a229acfaca4b63f01a1171b$$aMatt, Sonja$$b3$$udkfz 000127357 7001_ $$0P:(DE-He78)99ae95278bd95e30462a4fb2d12026c6$$aHofmann, Thomas$$b4$$udkfz 000127357 7001_ $$0P:(DE-He78)08a57258198dcedd8ff8ac7eef40341a$$aKyewski, Bruno$$b5$$udkfz 000127357 7001_ $$0P:(DE-HGF)0$$aDerbinski, Jens$$b6$$eLast author 000127357 773__ $$0PERI:(DE-600)1475085-5$$a10.4049/jimmunol.1402694$$gVol. 194, no. 3, p. 921 - 928$$n3$$p921 - 928$$tThe journal of immunology$$v194$$x1550-6606$$y2015 000127357 909CO $$ooai:inrepo02.dkfz.de:127357$$pVDB 000127357 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)83227bd2ef5cb3bccf76dc974c9ad2cc$$aDeutsches Krebsforschungszentrum$$b0$$kDKFZ 000127357 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-HGF)0$$aDeutsches Krebsforschungszentrum$$b1$$kDKFZ 000127357 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)8fc65269d45cda1a54ba654f7c0cf8ec$$aDeutsches Krebsforschungszentrum$$b2$$kDKFZ 000127357 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)ce86d7d02a229acfaca4b63f01a1171b$$aDeutsches Krebsforschungszentrum$$b3$$kDKFZ 000127357 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)99ae95278bd95e30462a4fb2d12026c6$$aDeutsches Krebsforschungszentrum$$b4$$kDKFZ 000127357 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)08a57258198dcedd8ff8ac7eef40341a$$aDeutsches Krebsforschungszentrum$$b5$$kDKFZ 000127357 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-HGF)0$$aDeutsches Krebsforschungszentrum$$b6$$kDKFZ 000127357 9131_ $$0G:(DE-HGF)POF3-314$$1G:(DE-HGF)POF3-310$$2G:(DE-HGF)POF3-300$$3G:(DE-HGF)POF3$$4G:(DE-HGF)POF$$aDE-HGF$$bGesundheit$$lKrebsforschung$$vTumor immunology$$x0 000127357 9141_ $$y2015 000127357 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS 000127357 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline 000127357 915__ $$0StatID:(DE-HGF)0310$$2StatID$$aDBCoverage$$bNCBI Molecular Biology Database 000127357 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bJ IMMUNOL : 2015 000127357 915__ $$0StatID:(DE-HGF)0600$$2StatID$$aDBCoverage$$bEbsco Academic Search 000127357 915__ $$0StatID:(DE-HGF)0030$$2StatID$$aPeer Review$$bASC 000127357 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bThomson Reuters Master Journal List 000127357 915__ $$0StatID:(DE-HGF)0110$$2StatID$$aWoS$$bScience Citation Index 000127357 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection 000127357 915__ $$0StatID:(DE-HGF)0111$$2StatID$$aWoS$$bScience Citation Index Expanded 000127357 915__ $$0StatID:(DE-HGF)1030$$2StatID$$aDBCoverage$$bCurrent Contents - Life Sciences 000127357 915__ $$0StatID:(DE-HGF)1050$$2StatID$$aDBCoverage$$bBIOSIS Previews 000127357 915__ $$0StatID:(DE-HGF)9900$$2StatID$$aIF < 5 000127357 9201_ $$0I:(DE-He78)D090-20160331$$kD090$$lEntwicklungsimmunologie$$x0 000127357 9201_ $$0I:(DE-He78)A210-20160331$$kA210$$lZelluläre Seneszenz$$x1 000127357 980__ $$ajournal 000127357 980__ $$aVDB 000127357 980__ $$aI:(DE-He78)D090-20160331 000127357 980__ $$aI:(DE-He78)A210-20160331 000127357 980__ $$aUNRESTRICTED