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 SOX9
Homo sapiens
 HIF1A
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Mus musculus
 PAX6
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 Snai2
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Transcription Factor Encyclopedia  BETA
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Overview

Forkhead box P1 (FOXP1) is one of four members of the FOXP subfamily of forkhead transcription factors [1][2]. The FOXP subfamily is somewhat atypical because of the C-terminal location of the forkhead domain and the N-terminal zinc finger and leucine zipper, which are required for transcriptional repression and both homo- and hetero-FOXP dimerisation [3].

The FOXP1 protein is widely but not ubiquitously expressed in human and murine tissues [2]. Studies on human FOXP1 have focused primarily on its role in human malignancy and in cellular differentiation [4]. The human FOXP1 gene maps to a candidate tumour suppressor locus at 3p14.1. Loss of FOXP1 has been reported in several types of carcinoma and this confers poor prognosis in breast cancer [5]. In contrast the FOXP1 locus is targeted by recurrent chromsome translocations [6] and amplifications in large B-cell lymphomas, where high level expression of FOXP1 correlates with a poor prognosis [7]. This may reflect expression of oncogenic smaller isoforms of the protein [8]. FOXP1 is also an autoantigen in eye disease and recent studies have implicated FOXP1 in human heart failure, mesenchymal stem cell renewal [9], osteoclast biology, and monocyte and macrophage differentiation [10].

Biochemical and molecular studies of murine Foxp1 have focussed on defining the functional domains of the protein, alternative splice forms, the Foxp1 DNA binding consensus and interacting proteins [3][11]. Studies using knockout mice have made a significant contribution by demonstrating that Foxp1 has an essential developmental role, involving cardiac [12], B-cell [13] and lung development, together with the coordination of neuron development in conjunction with Hox genes [14].

References
  1. Shu W et al. Characterization of a new subfamily of winged-helix/forkhead (Fox) genes that are expressed in the lung and act as transcriptional repressors. J. Biol. Chem., 276(29):27488-97. (PMID 11358962)
  2. Banham AH et al. The FOXP1 winged helix transcription factor is a novel candidate tumor suppressor gene on chromosome 3p. Cancer Res., 61(24):8820-9. (PMID 11751404)
  3. Li S et al. Transcriptional and DNA binding activity of the Foxp1/2/4 family is modulated by heterotypic and homotypic protein interactions. Mol. Cell. Biol., 24(2):809-22. (PMID 14701752)
  4. Koon HB et al. FOXP1: a potential therapeutic target in cancer. Expert Opin. Ther. Targets, 11(7):955-65. (PMID 17614763)
  5. Fox SB et al. Expression of the forkhead transcription factor FOXP1 is associated with estrogen receptor alpha and improved survival in primary human breast carcinomas. Clin. Cancer Res., 10(10):3521-7. (PMID 15161711)
  6. Streubel B et al. T(3;14)(p14.1;q32) involving IGH and FOXP1 is a novel recurrent chromosomal aberration in MALT lymphoma. Leukemia, 19(4):652-8. (PMID 15703784)
  7. Banham AH et al. Expression of the FOXP1 transcription factor is strongly associated with inferior survival in patients with diffuse large B-cell lymphoma. Clin. Cancer Res., 11(3):1065-72. (PMID 15709173)
  1. Brown PJ et al. Potentially oncogenic B-cell activation-induced smaller isoforms of FOXP1 are highly expressed in the activated B cell-like subtype of DLBCL. Blood, 111(5):2816-24. (PMID 18077790)
  2. Kubo H et al. Identification of mesenchymal stem cell (MSC)-transcription factors by microarray and knockdown analyses, and signature molecule-marked MSC in bone marrow by immunohistochemistry. Genes Cells, 14(3):407-24. (PMID 19228201)
  3. Shi C et al. Down-regulation of the forkhead transcription factor Foxp1 is required for monocyte differentiation and macrophage function. Blood, 112(12):4699-711. (PMID 18799727)
  4. Wang B et al. Multiple domains define the expression and regulatory properties of Foxp1 forkhead transcriptional repressors. J. Biol. Chem., 278(27):24259-68. (PMID 12692134)
  5. Wang B et al. Foxp1 regulates cardiac outflow tract, endocardial cushion morphogenesis and myocyte proliferation and maturation. Development, 131(18):4477-87. (PMID 15342473)
  6. Hu H et al. Foxp1 is an essential transcriptional regulator of B cell development. Nat. Immunol., 7(8):819-26. (PMID 16819554)
  7. Dasen JS et al. Hox repertoires for motor neuron diversity and connectivity gated by a single accessory factor, FoxP1. Cell, 134(2):304-16. (PMID 18662545)
Figures
FIGURE 1 FOXP1 overview
This figure provides a brief overview of the currently available data on human and murine FOXP1.
This figure was created by the authors of this article. The authors of this article have provided the assurance that this figure constitutes their original work.