|Forkhead box P1|
|Symbols||; 12CC4; QRF1; hFKH1B|
Forkhead box protein P1 is a protein that in humans is encoded by the FOXP1 gene. FOXP1 is necessary for the proper development of the brain and lung in mammals. It is a member of the large FOX family of transcription factors.
This gene belongs to subfamily P of the forkhead 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 both DNA-binding- and protein-protein binding-domains. This gene may act as a tumor 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.
Foxp1 is a transcription factor; specifically it is a transcriptional repressor. 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 cardiac myocyte maturation and proliferation, outflow tract separation of the pulmonary artery and aorta, and expression of Sox4 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. By knocking out Foxp1 scientists have discovered the importance of this gene in cardiac and lung development. Embryos without Foxp1 have severe defects in cardiac morphogenesis. A few of these defects include myocyte maturation and proliferation defects that cause a thin ventricular myocardial compact zone, non-separation of the pulmonary artery and aorta, and cardiomyocyte proliferation increase and defective differentiation. These defects, caused by Foxp1 inactivation, lead to fetal death.
It was shown that the embryonic stem cell (ESC)-specific isoform of FOXP1 stimulates the expression of transcription factor genes required for pluripotency, including OCT4, NANOG, NR5A2, and GDF3, 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 into induced 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.
The expression of FOXP1 was also implicated in the biology of B cell malignancies, and is regulated by by non-coding RNA (miRNA) termed miR-150. 
- "Entrez Gene: FOXP1 forkhead box P1".
- Gabut M, Samavarchi-Tehrani P, Wang X, Slobodeniuc V, O'Hanlon D, Sung HK, Alvarez M, Talukder S, Pan Q, Mazzoni EO, Nedelec S, Wichterle H, Woltjen K, Hughes TR, Zandstra PW, Nagy A, Wrana JL, Blencowe BJ (September 2011). "An alternative splicing switch regulates embryonic stem cell pluripotency and reprogramming". Cell 147 (1): 132–46. doi:10.1016/j.cell.2011.08.023. PMID 21924763.
- Mraz, M; Chen, L; Rassenti, L. Z.; Ghia, E. M.; Li, H; Jepsen, K; Smith, E. N.; Messer, K; Frazer, K. A.; Kipps, T. J. (2014). "MiR-150 influences B-cell receptor signaling in chronic lymphocytic leukemia by regulating expression of GAB1 and FOXP1". Blood 124 (1): 84–95. doi:10.1182/blood-2013-09-527234. PMID 24787006.
- Katoh M, Katoh M (2005). "Human FOX gene family (Review).". Int. J. Oncol. 25 (5): 1495–500. doi:10.3892/ijo.25.5.1495. PMID 15492844.
- Li C, Tucker PW (1994). "DNA-binding properties and secondary structural model of the hepatocyte nuclear factor 3/fork head domain.". Proc. Natl. Acad. Sci. U.S.A. 90 (24): 11583–7. doi:10.1073/pnas.90.24.11583. PMC 48028. PMID 8265594.
- Zhang QH, Ye M, Wu XY, (2001). "Cloning and functional analysis of cDNAs with open reading frames for 300 previously undefined genes expressed in CD34+ hematopoietic stem/progenitor cells". Genome Res. 10 (10): 1546–60. doi:10.1101/gr.140200. PMC 310934. PMID 11042152.
- Banham AH, Beasley N, Campo E, (2002). "The FOXP1 winged helix transcription factor is a novel candidate tumor suppressor gene on chromosome 3p". Cancer Res. 61 (24): 8820–9. PMID 11751404.
- Wolska MK, Bukowski K, Jakubczak A (2002). "[Occurrence of beta-lactamase type ESBL and IBL in Pseudomonas aeruginosa rods]". Medycyna doświadczalna i mikrobiologia 53 (1): 45–51. PMID 11757404.
- Strausberg RL, Feingold EA, Grouse LH, (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
- Wang B, Lin D, Li C, Tucker P (2003). "Multiple domains define the expression and regulatory properties of Foxp1 forkhead transcriptional repressors". J. Biol. Chem. 278 (27): 24259–68. doi:10.1074/jbc.M207174200. PMID 12692134.
- Li S, Weidenfeld J, Morrisey EE (2004). "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. doi:10.1128/MCB.24.2.809-822.2004. PMC 343786. PMID 14701752.
- Ota T, Suzuki Y, Nishikawa T, (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.
- Teramitsu I, Kudo LC, London SE, (2004). "Parallel FoxP1 and FoxP2 expression in songbird and human brain predicts functional interaction". J. Neurosci. 24 (13): 3152–63. doi:10.1523/JNEUROSCI.5589-03.2004. PMID 15056695.
- Fox SB, Brown P, Han C, (2004). "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. doi:10.1158/1078-0432.CCR-03-0461. PMID 15161711.
- Shi C, Zhang X, Chen Z, (2004). "Integrin engagement regulates monocyte differentiation through the forkhead transcription factor Foxp1". J. Clin. Invest. 114 (3): 408–18. doi:10.1172/JCI200421100. PMC 484980. PMID 15286807.
- Streubel B, Vinatzer U, Lamprecht A, (2005). "T(3;14)(p14.1;q32) involving IGH and FOXP1 is a novel recurrent chromosomal aberration in MALT lymphoma". Leukemia 19 (4): 652–8. doi:10.1038/sj.leu.2403644. PMID 15703784.
- Banham AH, Connors JM, Brown PJ, (2005). "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.
- Brown P, Marafioti T, Kusec R, Banham AH (2007). "The FOXP1 transcription factor is expressed in the majority of follicular lymphomas but is rarely expressed in classical and lymphocyte predominant Hodgkin's lymphoma". J. Mol. Histol. 36 (4): 249–56. doi:10.1007/s10735-005-6521-3. PMID 16200457.
- Giatromanolaki A, Koukourakis MI, Sivridis E, (2006). "Loss of expression and nuclear/cytoplasmic localization of the FOXP1 forkhead transcription factor are common events in early endometrial cancer: relationship with estrogen receptors and HIF-1alpha expression". Mod. Pathol. 19 (1): 9–16. doi:10.1038/modpathol.3800494. PMID 16258506.
- Sagaert X, de Paepe P, Libbrecht L, (2006). "Forkhead box protein P1 expression in mucosa-associated lymphoid tissue lymphomas predicts poor prognosis and transformation to diffuse large B-cell lymphoma". J. Clin. Oncol. 24 (16): 2490–7. doi:10.1200/JCO.2006.05.6150. PMID 16636337.
- Haralambieva E, Adam P, Ventura R, (2007). "Genetic rearrangement of FOXP1 is predominantly detected in a subset of diffuse large B-cell lymphomas with extranodal presentation". Leukemia 20 (7): 1300–3. doi:10.1038/sj.leu.2404244. PMID 16673020.
- Hannenhalli S, Putt ME, Gilmore JM, (2006). "Transcriptional genomics associates FOX transcription factors with human heart failure". Circulation 114 (12): 1269–76. doi:10.1161/CIRCULATIONAHA.106.632430. PMID 16952980.
- Weiguo Shu, Min Min Lu, Yuzhen Zhang, Philip W. Tucker, Deying Zhou, and Edward E. Morrisey. Foxp2 and Foxp1 cooperatively regulate lung and esophagus development. Development 2007 134:1991-2000; published ahead of print April 11, 2007, doi:10.1242/dev.02846
- Bin Wang, Joel Weidenfeld, Min Min Lu, Shanna Maika, William A. Kuziel, Edward E. Morrisey, and Philip W. Tucker. Foxp1 regulates cardiac outflow tract, endocardial cushion morphogenesis and myocyte proliferation and maturation. Development 2004 131:4477-4487; doi:10.1242/dev.01287