The FOX family of transcription factors is a large group of proteins that share a common DNA binding domain termed a winged-helix or forkhead domain. During early development, FOXP1 and FOXP2 are expressed abundantly in the lung, with lower levels of expression in neural, intestinal and cardiovascular tissues, where they act as transcription repressors. FOXP1 is widely expressed in adult tissues, while neoplastic cells often exhibit a dramatic change in expression level or localization of FOXP1. The gene encoding human FOXP1 maps to chromosome 3p14.1, and the gene encoding human FOXP2 maps to chromosome 7q31. The gene encoding FOXP3, a third member of this family, maps to chromosome Xp11.23. Mutations in this gene cause IPEX, a fatal, X-linked inherited disorder characterized by immune dysregulation. The FOXP3 protein, also known as scurfin, is essential for normal immune homeostasis. Specifically, FOXP3 represses transcription through a DNA binding forkhead domain, thereby regulating T cell activation.
Background References
1. Nguyen N et al. Tumor infiltrating lymphocytes and survival in patients with head and neck squamous cell carcinoma. Head Neck 38:1074-84 (2016).
2. Gu L et al. Rapamycin ameliorates CCl4-induced liver fibrosis in mice through reciprocal regulation of the Th17/Treg cell balance. Mol Med Rep 14:1153-61 (2016).
Post-translational Modification
Polyubiquitinated, leading to its proteasomal degradation in regulatory T-cells (Treg) which is mediated by STUB1 in a HSPA1A/B-dependent manner. Deubiquitinated by USP7 leading to increase in protein stability.; Phosphorylation at Ser-418 regulates its transcriptional repressor activity and consequently, regulatory T-cells (Treg) suppressive function. Dephosphorylated at Ser-418 by protein phosphatase 1 (PP1) in Treg cells derived from patients with rheumatoid arthritis. Phosphorylation by CDK2 negatively regulates its transcriptional activity and protein stability (By similarity).; Acetylation on lysine residues stabilizes FOXP3 and promotes differentiation of T-cells into induced regulatory T-cells (iTregs) associated with suppressive functions. Deacetylated by SIRT1.; Undergoes proteolytic cleavage in activated regulatory T-cells (Treg), and can be cleaved at either the N- or C-terminal site, or at both sites.
Immunohistochemical analysis of paraffin-embedded human lymph node tissue with Rabbit anti-FOXP3 antibody (ET1702-16) at 1/200 dilution.
The section was pre-treated using heat mediated antigen retrieval with sodium citrate buffer (pH 6.0) (high pressure) for 2 minutes. The tissues were blocked in 1% BSA for 20 minutes at room temperature, washed with ddH2O and PBS, and then probed with the primary antibody (ET1702-16) at 1/200 dilution for 1 hour at room temperature. The detection was performed using an HRP conjugated compact polymer system. DAB was used as the chromogen. Tissues were counterstained with hematoxylin and mounted with DPX.
Immunohistochemical analysis of paraffin-embedded human tonsil tissue with Rabbit anti-FOXP3 antibody (ET1702-16) at 1/200 dilution.
The section was pre-treated using heat mediated antigen retrieval with sodium citrate buffer (pH 6.0) (high pressure) for 2 minutes. The tissues were blocked in 1% BSA for 20 minutes at room temperature, washed with ddH2O and PBS, and then probed with the primary antibody (ET1702-16) at 1/200 dilution for 1 hour at room temperature. The detection was performed using an HRP conjugated compact polymer system. DAB was used as the chromogen. Tissues were counterstained with hematoxylin and mounted with DPX.
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