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.
Function
[edit]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]
See also
[edit]References
[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 (November 2012). "The distinct and overlapping phenotypic spectra of FOXP1 and FOXP2 in cognitive disorders". Human Genetics. 131 (11): 1687–1698. 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, et al. (September 2011). "An alternative splicing switch regulates embryonic stem cell pluripotency and reprogramming". Cell. 147 (1): 132–146. doi:10.1016/j.cell.2011.08.023. PMID 21924763. S2CID 4978953.
Further reading
[edit]- Katoh M, Katoh M (November 2004). "Human FOX gene family (Review)". International Journal of Oncology. 25 (5): 1495–1500. doi:10.3892/ijo.25.5.1495. PMID 15492844.
- Li C, Tucker PW (December 1993). "DNA-binding properties and secondary structural model of the hepatocyte nuclear factor 3/fork head domain". Proceedings of the National Academy of Sciences of the United States of America. 90 (24): 11583–11587. Bibcode:1993PNAS...9011583L. doi:10.1073/pnas.90.24.11583. PMC 48028. PMID 8265594.
- Zhang QH, Ye M, Wu XY, Ren SX, Zhao M, Zhao CJ, et al. (October 2000). "Cloning and functional analysis of cDNAs with open reading frames for 300 previously undefined genes expressed in CD34+ hematopoietic stem/progenitor cells". Genome Research. 10 (10): 1546–1560. doi:10.1101/gr.140200. PMC 310934. PMID 11042152.
- 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. 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 (July 2003). "Multiple domains define the expression and regulatory properties of Foxp1 forkhead transcriptional repressors". The Journal of Biological Chemistry. 278 (27): 24259–24268. doi:10.1074/jbc.M207174200. PMID 12692134.
- Li S, Weidenfeld J, Morrisey EE (January 2004). "Transcriptional and DNA binding activity of the Foxp1/2/4 family is modulated by heterotypic and homotypic protein interactions". Molecular and Cellular Biology. 24 (2): 809–822. doi:10.1128/MCB.24.2.809-822.2004. PMC 343786. PMID 14701752.
- Teramitsu I, Kudo LC, London SE, Geschwind DH, White SA (March 2004). "Parallel FoxP1 and FoxP2 expression in songbird and human brain predicts functional interaction". The Journal of Neuroscience. 24 (13): 3152–3163. doi:10.1523/JNEUROSCI.5589-03.2004. PMC 6730014. PMID 15056695.
- Fox SB, Brown P, Han C, Ashe S, Leek RD, Harris AL, et al. (May 2004). "Expression of the forkhead transcription factor FOXP1 is associated with estrogen receptor alpha and improved survival in primary human breast carcinomas". Clinical Cancer Research. 10 (10): 3521–3527. doi:10.1158/1078-0432.CCR-03-0461. PMID 15161711.
- Shi C, Zhang X, Chen Z, Sulaiman K, Feinberg MW, Ballantyne CM, et al. (August 2004). "Integrin engagement regulates monocyte differentiation through the forkhead transcription factor Foxp1". The Journal of Clinical Investigation. 114 (3): 408–418. doi:10.1172/JCI21100. PMC 484980. PMID 15286807.
- Streubel B, Vinatzer U, Lamprecht A, Raderer M, Chott A (April 2005). "T(3;14)(p14.1;q32) involving IGH and FOXP1 is a novel recurrent chromosomal aberration in MALT lymphoma". Leukemia. 19 (4): 652–658. doi:10.1038/sj.leu.2403644. PMID 15703784.
- Banham AH, Connors JM, Brown PJ, Cordell JL, Ott G, Sreenivasan G, et al. (February 2005). "Expression of the FOXP1 transcription factor is strongly associated with inferior survival in patients with diffuse large B-cell lymphoma". Clinical Cancer Research. 11 (3): 1065–1072. doi:10.1158/1078-0432.1065.11.3. PMID 15709173.
- 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. PMID 16200457. S2CID 10290316.
- Giatromanolaki A, Koukourakis MI, Sivridis E, Gatter KC, Harris AL, Banham AH (January 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". Modern Pathology. 19 (1): 9–16. doi:10.1038/modpathol.3800494. PMID 16258506.
- 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. PMID 16636337.
- Haralambieva E, Adam P, Ventura R, Katzenberger T, Kalla J, Höller S, et al. (July 2006). "Genetic rearrangement of FOXP1 is predominantly detected in a subset of diffuse large B-cell lymphomas with extranodal presentation". Leukemia. 20 (7): 1300–1303. doi:10.1038/sj.leu.2404244. PMID 16673020.
- Hannenhalli S, Putt ME, Gilmore JM, Wang J, Parmacek MS, Epstein JA, et al. (September 2006). "Transcriptional genomics associates FOX transcription factors with human heart failure". Circulation. 114 (12): 1269–1276. doi:10.1161/CIRCULATIONAHA.106.632430. PMID 16952980.
- Shu W, Lu MM, Zhang Y, Tucker PW, Zhou D, Morrisey EE (May 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, Lu MM, Maika S, Kuziel WA, Morrisey EE, et al. (September 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
[edit]- 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+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.
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