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@ARTICLE{Rattay:127357,
      author       = {K. Rattay$^*$ and J. Claude$^*$ and E. Rezavandy$^*$ and S.
                      Matt$^*$ and T. Hofmann$^*$ and B. Kyewski$^*$ and J.
                      Derbinski$^*$},
      title        = {{H}omeodomain-interacting protein kinase 2, a novel
                      autoimmune regulator interaction partner, modulates
                      promiscuous gene expression in medullary thymic epithelial
                      cells.},
      journal      = {The journal of immunology},
      volume       = {194},
      number       = {3},
      issn         = {1550-6606},
      address      = {Bethesda, Md.},
      publisher    = {Soc.},
      reportid     = {DKFZ-2017-03382},
      pages        = {921 - 928},
      year         = {2015},
      abstract     = {Promiscuous 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.},
      keywords     = {APECED protein (NLM Chemicals) / Antigens (NLM Chemicals) /
                      Carrier Proteins (NLM Chemicals) / Transcription Factors
                      (NLM Chemicals) / HIPK2 protein, human (NLM Chemicals) /
                      Hipk2 protein, mouse (NLM Chemicals) /
                      Protein-Serine-Threonine Kinases (NLM Chemicals)},
      cin          = {D090 / A210},
      ddc          = {610},
      cid          = {I:(DE-He78)D090-20160331 / I:(DE-He78)A210-20160331},
      pnm          = {314 - Tumor immunology (POF3-314)},
      pid          = {G:(DE-HGF)POF3-314},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:25552543},
      doi          = {10.4049/jimmunol.1402694},
      url          = {https://inrepo02.dkfz.de/record/127357},
}