Forkhead box protein P1 is aprotein that in humans is encoded by theFOXP1gene. FOXP1 is necessary for the proper development of the brain, heart, and lung inmammals. It is a member of the largeFOX family oftranscription factors.
This gene belongs to subfamily P of theforkhead box (FOX) transcription factor family. Forkhead box transcription factors play important roles in the regulation of tissue- and cell type-specific gene transcription during both development and adulthood. Forkhead box P1 protein contains bothDNA-binding- and protein-protein binding-domains. This gene may act as atumor suppressor as it is lost in several tumor types and maps to a chromosomal region (3p14.1) reported to contain a tumor suppressor gene(s). Alternative splicing results in multiple transcript variants encoding different isoforms.[3]
Foxp1 is a transcription factor; specifically it is a transcriptionalrepressor. Fox genes are part of a forkhead DNA-binding domain family. This domain binds to sequences in promoters and enhancers of many genes. Foxp1 regulates a variety of important aspects of development including tissue development of: the lungs, brain, thymus and heart. In the heart Foxp1 has 3 vital roles, these include the regulation of cardiacmyocyte maturation and proliferation, outflow tract separation of thepulmonary artery andaorta, and expression ofSox4 in cushions and myocardium. Foxp1 is also an important gene in muscle development of the esophagus and esophageal epithelium. Foxp1 is also an important regulator of lung airway morphogenesis. Foxp1knockout embryos display severe defects in cardiacmorphogenesis. A few of these defects includemyocyte maturation and proliferation defects that cause a thin ventricular myocardial compact zone, non-separation of thepulmonary artery andaorta, andcardiomyocyte proliferation increase and defective differentiation. These defects, caused by Foxp1 inactivation, lead to fetal death. Disruptions of FoxP1 have been identified in very rare human patients and – similarly to FoxP2 - lead to cognitive dysfunction, including intellectual disability andautism spectrum disorder, together with language impairment.[4]
It was shown that theembryonic stem cell (ESC)-specific isoform of FOXP1 stimulates the expression of transcription factor genes required forpluripotency, includingOCT4,NANOG,NR5A2, andGDF3, while concomitantly repressing genes required for ESC differentiation. This isoform also promotes the maintenance of ESC pluripotency and contributes to efficient reprogramming of somatic cells intoinduced pluripotent stem cells. These results reveal a pivotal role for an Alternative splicing event in the regulation of pluripotency through the control of critical ESC-specific transcriptional programs.[5]
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Banham AH, Beasley N, Campo E, Fernandez PL, Fidler C, Gatter K, et al. (December 2001). "The FOXP1 winged helix transcription factor is a novel candidate tumor suppressor gene on chromosome 3p".Cancer Research.61 (24):8820–8829.PMID11751404.
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Brown P, Marafioti T, Kusec R, Banham AH (May 2005). "The FOXP1 transcription factor is expressed in the majority of follicular lymphomas but is rarely expressed in classical and lymphocyte predominant Hodgkin's lymphoma".Journal of Molecular Histology.36 (4):249–256.doi:10.1007/s10735-005-6521-3.PMID16200457.S2CID10290316.
Sagaert X, de Paepe P, Libbrecht L, Vanhentenrijk V, Verhoef G, Thomas J, et al. (June 2006). "Forkhead box protein P1 expression in mucosa-associated lymphoid tissue lymphomas predicts poor prognosis and transformation to diffuse large B-cell lymphoma".Journal of Clinical Oncology.24 (16):2490–2497.doi:10.1200/JCO.2006.05.6150.PMID16636337.
