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Cutting Edge: a novel, human-specific interacting protein couples FOXP3 to a chromatin-remodeling complex that contains KAP1/TRIM28.

  • Author(s): Huang, Chunjian
  • Martin, Sunil
  • Pfleger, Christian
  • Du, Jianguang
  • Buckner, Jane H
  • Bluestone, Jeffrey A
  • Riley, James L
  • Ziegler, Steven F
  • et al.

Regulatory T cells (Tregs) play a pivotal role in the maintenance of immunological self-tolerance. Deficiency or dysfunction of Tregs leads to severe autoimmune diseases. Although the forkhead/winged-helix family member FOXP3 is critical for Treg differentiation and function, the molecular basis for FOXP3 function remains unclear. In this study, we identified and characterized a human-specific FOXP3-interacting protein, referred to as FIK (FOXP3-interacting KRAB domain-containing protein). FIK is highly expressed in Tregs and acts as a bridging molecule to link FOXP3 with the chromatin-remodeling scaffold protein KAP1 (TIF-1β/TRIM28). Disruption of the FOXP3-FIK-KAP1 complex in Tregs restored expression of FOXP3-target genes and abrogated the suppressor activity of the Tregs. These data demonstrate a critical role for FIK in regulating FOXP3 activity and Treg function.

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