Forkhead box protein P1 is a protein that in humans is encoded by the FOXP1gene. FOXP1 is necessary for the proper development of the brain, heart, 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.[3]
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. Foxp1 knockout embryos display 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. Disruptions of FoxP1 have been identified in very rare human patients and – similarly to FoxP2 - lead to cognitive dysfunction, including intellectual disability and autism spectrum disorder, together with language impairment.[4]
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.[5]
^Bacon C, Rappold GA (Nov 2012). "The distinct and overlapping phenotypic spectra of FOXP1 and FOXP2 in cognitive disorders". Human Genetics. 131 (11): 1687–98. doi:10.1007/s00439-012-1193-z. PMC3470686. PMID 22736078.
^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. S2CID 4978953.
Further readingedit
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. PMC48028. PMID 8265594.
Zhang QH, Ye M, Wu XY, Ren SX, Zhao M, Zhao CJ, Fu G, Shen Y, Fan HY, Lu G, Zhong M, Xu XR, Han ZG, Zhang JW, Tao J, Huang QH, Zhou J, Hu GX, Gu J, Chen SJ, Chen Z (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. PMC310934. PMID 11042152.
Banham AH, Beasley N, Campo E, Fernandez PL, Fidler C, Gatter K, Jones M, Mason DY, Prime JE, Trougouboff P, Wood K, Cordell JL (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.
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. PMC343786. PMID 14701752.
Teramitsu, Ikuko; Kudo, Lili C.; London, Sarah E.; Geschwind, Daniel H.; White, Stephanie A. (31 March 2004). "Parallel FoxP1 and FoxP2 Expression in Songbird and Human Brain Predicts Functional Interaction". Journal of Neuroscience. 24 (13): 3152–3163. doi:10.1523/JNEUROSCI.5589-03.2004. ISSN 0270-6474. PMC6730014. PMID 15056695.
Fox SB, Brown P, Han C, Ashe S, Leek RD, Harris AL, Banham AH (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, Sulaiman K, Feinberg MW, Ballantyne CM, Jain MK, Simon DI (2004). "Integrin engagement regulates monocyte differentiation through the forkhead transcription factor Foxp1". J. Clin. Invest. 114 (3): 408–18. doi:10.1172/JCI21100. PMC484980. PMID 15286807.
Streubel B, Vinatzer U, Lamprecht A, Raderer M, Chott 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, Cordell JL, Ott G, Sreenivasan G, Farinha P, Horsman DE, Gascoyne RD (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. doi:10.1158/1078-0432.1065.11.3. 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. S2CID 10290316.
Giatromanolaki A, Koukourakis MI, Sivridis E, Gatter KC, Harris AL, Banham AH (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, Vanhentenrijk V, Verhoef G, Thomas J, Wlodarska I, De Wolf-Peeters C (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, Katzenberger T, Kalla J, Höller S, Hartmann M, Rosenwald A, Greiner A, Muller-Hermelink HK, Banham AH, Ott G (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, Wang J, Parmacek MS, Epstein JA, Morrisey EE, Margulies KB, Cappola TP (2006). "Transcriptional genomics associates FOX transcription factors with human heart failure". Circulation. 114 (12): 1269–76. doi:10.1161/CIRCULATIONAHA.106.632430. PMID 16952980.
Shu W, Min Lu M, Zhang Y, Tucker PW, Zhou D, Morrisey EE (2007). "Foxp2 and Foxp1 cooperatively regulate lung and esophagus development". Development. 134 (10): 1991–2000. doi:10.1242/dev.02846. PMID 17428829.
Wang B, Weidenfeld J, Min Lu M, Maika S, Kuziel WA, Morrisey EE, Tucker PW (2004). "Foxp1 regulates cardiac outflow tract, endocardial cushion morphogenesis and myocyte proliferation and maturation". Development. 131 (18): 4477–4487. doi:10.1242/dev.01287. PMID 15342473.
External linksedit
Further clinical details at OMIM Entry #613670 (Mental Retardation With Language Impairment and with or without Autistic Features)
Additional information also at OMIM Entry #605515 (Forkhead Box P1)
foxp1, forkhead, protein, protein, that, humans, encoded, gene, necessary, proper, development, brain, heart, lung, mammals, member, large, family, transcription, factors, available, structurespdbhuman, uniprot, search, pdbe, rcsblist, codes2kiuidentifiersalia. 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 heart and lung in mammals It is a member of the large FOX family of transcription factors FOXP1Available structuresPDBHuman UniProt search PDBe RCSBList of PDB id codes2KIUIdentifiersAliasesFOXP1 12CC4 HSPC215 MFH QRF1 hFKH1B forkhead box P1External IDsOMIM 605515 HomoloGene 136512 GeneCards FOXP1Gene location Human Chr Chromosome 3 human 1 Band3p13Start70 954 693 bp 1 End71 583 978 bp 1 RNA expression patternBgeeHumanMouse ortholog Top expressed inpancreatic ductal cellcardiasaphenous veinpyloruspericardiumurethralactiferous ductvena cavaendothelial cellparotid glandn aMore reference expression dataBioGPSn aGene ontologyMolecular functionmetal ion binding sequence specific DNA binding protein self association androgen receptor binding DNA binding transcription factor activity DNA binding protein binding identical protein binding DNA binding transcription factor activity RNA polymerase II specific RNA polymerase II cis regulatory region sequence specific DNA binding chromatin binding transcription factor activity RNA polymerase II distal enhancer sequence specific binding transcription factor binding protein homodimerization activity protein heterodimerization activityCellular componentnucleus nucleoplasm cytoplasmBiological processregulation of monocyte differentiation negative regulation of androgen receptor signaling pathway negative regulation of B cell apoptotic process positive regulation of endothelial cell migration transcription DNA templated response to lipopolysaccharide regulation of defense response to bacterium endothelial cell activation regulation of endothelial tube morphogenesis macrophage activation osteoclast development positive regulation of smooth muscle cell proliferation T follicular helper cell differentiation regulation of macrophage colony stimulating factor production regulation of tumor necrosis factor production regulation of inflammatory response osteoclast differentiation monocyte activation regulation of transcription DNA templated negative regulation of transcription DNA templated regulation of transcription by RNA polymerase II somatic stem cell population maintenance negative regulation of transcription by RNA polymerase II in utero embryonic development positive regulation of mesenchymal cell proliferation pre B cell differentiation positive regulation of immunoglobulin production heart development skeletal muscle tissue development motor neuron axon guidance ventral spinal cord development striatum development lung development forebrain development immunoglobulin V D J recombination response to testosterone sarcomere organization positive regulation of transcription DNA templated positive regulation of transcription by RNA polymerase II smooth muscle tissue development positive regulation of epithelial cell proliferation cardiac muscle cell differentiation regulation of cardiac muscle cell proliferation negative regulation of cell growth involved in cardiac muscle cell development lung secretory cell differentiation cellular response to tumor necrosis factor innate vocalization behavior regulation of action potential regulation of lung goblet cell differentiation negative regulation of lung goblet cell differentiation cellular response to ionomycin positive regulation of hydrogen peroxide induced cell death positive regulation of cardiac muscle cell differentiation cellular response to DNA damage stimulus negative regulation of gene expression positive regulation of B cell receptor signaling pathwaySources Amigo QuickGOOrthologsSpeciesHumanMouseEntrez27086n aEnsemblENSG00000114861n aUniProtQ9H334n aRefSeq mRNA NM 001012505NM 001244808NM 001244810NM 001244812NM 001244813NM 001244814NM 001244815NM 001244816NM 032682NM 001349338NM 001349340NM 001349341NM 001349342NM 001349343NM 001349344NM 001349337NM 001370548n aRefSeq protein NP 001012523NP 001231737NP 001231739NP 001231741NP 001231742NP 001231743NP 001231744NP 001231745NP 116071NP 001336267NP 001336269NP 001336270NP 001336271NP 001336272NP 001336273NP 001336266n aLocation UCSC Chr 3 70 95 71 58 Mbn aPubMed search 2 n aWikidataView Edit Human Contents 1 Function 2 See also 3 References 4 Further reading 5 External linksFunction editThis 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 3 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 Foxp1 knockout embryos display 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 Disruptions of FoxP1 have been identified in very rare human patients and similarly to FoxP2 lead to cognitive dysfunction including intellectual disability and autism spectrum disorder together with language impairment 4 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 5 See also editFOXP2 FOXP3References edit a b c GRCh38 Ensembl release 89 ENSG00000114861 Ensembl May 2017 Human PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Entrez Gene FOXP1 forkhead box P1 Bacon C Rappold GA Nov 2012 The distinct and overlapping phenotypic spectra of FOXP1 and FOXP2 in cognitive disorders Human Genetics 131 11 1687 98 doi 10 1007 s00439 012 1193 z PMC 3470686 PMID 22736078 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 S2CID 4978953 Further reading editKatoh 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 Ren SX Zhao M Zhao CJ Fu G Shen Y Fan HY Lu G Zhong M Xu XR Han ZG Zhang JW Tao J Huang QH Zhou J Hu GX Gu J Chen SJ Chen Z 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 Fernandez PL Fidler C Gatter K Jones M Mason DY Prime JE Trougouboff P Wood K Cordell JL 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 doswiadczalna i mikrobiologia 53 1 45 51 PMID 11757404 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 Teramitsu Ikuko Kudo Lili C London Sarah E Geschwind Daniel H White Stephanie A 31 March 2004 Parallel FoxP1 and FoxP2 Expression in Songbird and Human Brain Predicts Functional Interaction Journal of Neuroscience 24 13 3152 3163 doi 10 1523 JNEUROSCI 5589 03 2004 ISSN 0270 6474 PMC 6730014 PMID 15056695 Fox SB Brown P Han C Ashe S Leek RD Harris AL Banham AH 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 Sulaiman K Feinberg MW Ballantyne CM Jain MK Simon DI 2004 Integrin engagement regulates monocyte differentiation through the forkhead transcription factor Foxp1 J Clin Invest 114 3 408 18 doi 10 1172 JCI21100 PMC 484980 PMID 15286807 Streubel B Vinatzer U Lamprecht A Raderer M Chott 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 Cordell JL Ott G Sreenivasan G Farinha P Horsman DE Gascoyne RD 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 doi 10 1158 1078 0432 1065 11 3 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 S2CID 10290316 Giatromanolaki A Koukourakis MI Sivridis E Gatter KC Harris AL Banham AH 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 Vanhentenrijk V Verhoef G Thomas J Wlodarska I De Wolf Peeters C 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 Katzenberger T Kalla J Holler S Hartmann M Rosenwald A Greiner A Muller Hermelink HK Banham AH Ott G 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 Wang J Parmacek MS Epstein JA Morrisey EE Margulies KB Cappola TP 2006 Transcriptional genomics associates FOX transcription factors with human heart failure Circulation 114 12 1269 76 doi 10 1161 CIRCULATIONAHA 106 632430 PMID 16952980 Shu W Min Lu M Zhang Y Tucker PW Zhou D Morrisey EE 2007 Foxp2 and Foxp1 cooperatively regulate lung and esophagus development Development 134 10 1991 2000 doi 10 1242 dev 02846 PMID 17428829 Wang B Weidenfeld J Min Lu M Maika S Kuziel WA Morrisey EE Tucker PW 2004 Foxp1 regulates cardiac outflow tract endocardial cushion morphogenesis and myocyte proliferation and maturation Development 131 18 4477 4487 doi 10 1242 dev 01287 PMID 15342473 External links editFurther clinical details at OMIM Entry 613670 Mental Retardation With Language Impairment and with or without Autistic Features Additional information also at OMIM Entry 605515 Forkhead Box P1 FOXP1 protein human at the U S National Library of Medicine Medical Subject Headings MeSH Overview of all the structural information available in the PDB for UniProt Q9H334 Forkhead box protein P1 at the PDBe KB Information for families and people impacted by FOXP1 syndrome can be found at the International FOXP1 Foundation site This article incorporates text from the United States National Library of Medicine which is in the public domain Retrieved from https en wikipedia org w index php title FOXP1 amp oldid 1136170941, wikipedia, wiki, book, books, library,
