Atlas of Genetics and Cytogenetics in Oncology and Haematology
FOXP1 (Forkhead box P1)
| Identity |
| Other names | 12CC4 |
| FLJ23741 | |
| hFKH1B | |
| HSPC215 | |
| MGC12942 | |
| MGC88572 | |
| MGC9551 | |
| QRF1 (Glutamine-Rich Factor 1) | |
| Hugo | FOXP1 |
| Location | 3p14.1 |
| Local_order | 3ptelomere-3' FOXP1 5'-centromere |
 | |
| FOXP1 (3p14.1): RP11-154H23 (Spectrum0range) and RP11-79P21 (SpectrumGreen) covering the 5' and the 3'end of FOXP1, respectively. | |
| Note | chr3: 71087426-71715830 bps |
| DNA/RNA |
| Description | 21 exons; the first 5 exons, the 5' part of exon 6 and the 3' part of exon 21 are non-coding. |
| Transcription | 628405 bps mRNA; transcribed in a centromeric to telomeric orientation. Alternative splicing; 4 named isoforms (Q9H334-1,-2,-3,-4) recognized. |
| Protein |
 | |
| Schematic diagram of the Foxp1 protein indicating the localization of predicted domains and motifs. Modified from Banham AH et al., Cancer Res 61, 8820-8820, 2001. | |
| Note | Forkhead box P1 |
| Description | The FOXP1 protein is 677-amino acid long and its molecular weight is 75317 Da. It contains two potential nucleic acid-binding motifs, including a forkhead (winged-helix) domain and C2H2 zinc finger domain. Other regions that may regulate transcription and mediate protein-protein interaction include coiled-coil, glutamine rich, S/T-rich, S/T/P-rich and acidic rich domains. Two potential nuclear localization signals (NLS) were identified at amino acid434-440 and amino acid543-546. Two potential PEST motifs are predicted in the acidic region near its COOH terminus. The FOXP1 protein contains a number potential of cyclin-cdk phosphorylation sites and a recognition site for the p70S6-kinase which is itself regulated by the PI(3)K. The FOXP1 protein forms homodimers and heterodimers with FOXP2 and FOXP4. Dimerization is required for DNA-binding. |
| Expression | Ubiquitous expression in normal adult and fetal human tissues; highest expression in lymphoid and gastrointestinal tissues. Within the B lineage, FOXP1 is expressed modestly in progenitors, with highest levels in activated B cells and mantle zone B cells. |
| Localisation | Predominantly nuclear |
| Function | FOXP1 can act as a transcriptional repressor. The gene has a broad range of functions and plays an important role in cardiac and lung development, B-cell development and macrophage differentiation. FOXP1 is implicated in malignancy. |
| Homology | Member of the broadly expressed FOXP subfamily which itself is a part of the FOX gene family of transcription factors, characterized by sharing a common DNA binding domain termed forkhead or a winged-helix domain. FOXP proteins (FOXP1, -2, -3, -4) play important roles in immune responses, organ development and cancer pathogenesis. |
| Implicated in |
| Entity | t(3;9)(p14;p13) --> PAX5-FOXP1 in childhood ALL |
| Disease | B-progenitor ALL (single case) |
| Cytogenetics | Unknown |
| Abnormal Protein | Contains the NH2 terminus of PAX5 with the DNA-binding paired, octapeptide and homeodomain-like domains and the COOH-terminus of FOXP1 containing its DNA-binding (Zn and FH) and transcriptional regulatory domains. |
| Oncogenesis | The fusion protein is predicted to retain the ability to bind to PAX5 and FOXP1 transcriptional targets, but no longer provide normal transcriptional regulatory functions of both genes. |
| Entity | t(3;14)(p14;q32)/B-cell malignancies IGH-FOXP1 |
| Disease | t(3;14)(p14;q32) resulting in upregulated expression of FOXP1, is a rare aberration in B-NHL. The translocation occurs recurrently in MALT-type of marginal zone B-cell lymphomas (MZBCL) and diffuse large B cell lymphoma (DLBCL). Single cases with variant FOXP1 translocations involving unknown non-IG loci have been reported. Of note, a significant number of DLBCL (with a predominantly ABC-like phenotype) and extranodal MZBCL displayed a strong expression of FOXP1 which is independent of genomic rearrangements of the FOXP1 locus. FOXP1-positivity was also found in numerous cases of cutaneous B-cell lymphomas and follicular lymphomas. |
| Prognosis | High expression of FOXP1 in DLBCL is associated with poor prognosis. Deregulation of FOXP1 in MALT lymphomas possibly leads to transformation to a more aggressive DLBCL. |
| Cytogenetics | t(3;14) was recorded as a sole aberration and as a part of complex karyotypes. In MALT lymphomas, translocations involving FOXP1, MALT1 and BCL10 are mutually exclusive. |
| Hybrid/Mutated Gene | No hybrid gene; 5' FOXP1 juxtaposed with 3' IGH enhancer. Molecular characteristics of FOXP1 variant translocations are unknown. |
| Oncogenesis | The occurrence of activated FOXP1 translocations in lymphoma indicates that FOXP1 functions as an oncogene. So far, mechanisms and molecular consequences of aberrant expression of FOXP1 in lymphomas not harboring 3p14/FOXP1 rearrangements are unknown. The preliminary data suggest that not the full-length protein, but smaller FOXP1 isoforms are atypically highly expressed in ABC-DLBCL cell lines. Their role in the disease process is currently investigated. |
| Entity | Solid tumors |
| Disease | FOXP1 abnormalities (overexpression, mislocalization or loss of FOXP1) are observed in a wide variety of cancers, particularly of epithelial origin. FOXP1 located in the 3p region frequently deleted in multiple types of cancers is one of a few potential tumor suppressor genes. Genomic loss of FOXP1 correlates with a decrease in FOXP1 mRNA and/or a decrease in FOXP1 protein levels in a significant number of analyzed lung cancers and head and neck cancers. In addition, an aberrant cytoplasmic localization of FOXP1 has been observed in a number of epithelial malignancies. Whether that aberrant localization may be a mechanism for inactivation of FOXP1 remains to be determined. So far, the direct evidence that FOXP1 functions as a tumor suppressor gene is limited. In contrast, increased nuclear expression of FOXP1 has been detected in renal cell carcinoma, some prostate cancers, endometrial cancers and breast cancers. The mechanisms leading to altered expression of FOXP1 in cancer are elusive. |
| Breakpoints |
 | |
| Recurrent (14q32/IGH) and non-recurrent chromosomal breakpoints/partners involved in the FOXP1 rearrangements in hematological malignancies. | |
| External links |
| Bibliography |
| DNA-binding properties and secondary structural model of the hepatocyte nuclear factor 3/fork head domain. |
| Li C, Tucker PW |
| Proceedings of the National Academy of Sciences of the United States of America. 1993 ; 90 (24) : 11583-11587. |
| PMID 8265594 |
| The FOXP1 winged helix transcription factor is a novel candidate tumor suppressor gene on chromosome 3p. |
| Banham AH, Beasley N, Campo E, Fernandez PL, Fidler C, Gatter K, Jones M, Mason DY, Prime JE, Trougouboff P, Wood K, Cordell JL |
| Cancer research. 2001 ; 61 (24) : 8820-8829. |
| PMID 11751404 |
| Forkhead transcription factors: key players in development and metabolism. |
| Carlsson P, Mahlapuu M |
| Developmental biology. 2002 ; 250 (1) : 1-23. |
| PMID 12297093 |
| Multiple domains define the expression and regulatory properties of Foxp1 forkhead transcriptional repressors. |
| Wang B, Lin D, Li C, Tucker P |
| The Journal of biological chemistry. 2003 ; 278 (27) : 24259-24268. |
| PMID 12692134 |
| Strong expression of FOXP1 identifies a distinct subset of diffuse large B-cell lymphoma (DLBCL) patients with poor outcome. |
| Barrans SL, Fenton JA, Banham A, Owen RG, Jack AS |
| Blood. 2004 ; 104 (9) : 2933-2935. |
| PMID 15238418 |
| Expression of the forkhead transcription factor FOXP1 is associated with estrogen receptor alpha and improved survival in primary human breast carcinomas. |
| Fox SB, Brown P, Han C, Ashe S, Leek RD, Harris AL, Banham AH |
| Clinical cancer research : an official journal of the American Association for Cancer Research. 2004 ; 10 (10) : 3521-3527. |
| PMID 15161711 |
| Human FOX gene family (Review). |
| Katoh M, Katoh M |
| International journal of oncology. 2004 ; 25 (5) : 1495-1500. |
| PMID 15492844 |
| Integrin engagement regulates monocyte differentiation through the forkhead transcription factor Foxp1. |
| Shi C, Zhang X, Chen Z, Sulaiman K, Feinberg MW, Ballantyne CM, Jain MK, Simon DI |
| The Journal of clinical investigation. 2004 ; 114 (3) : 408-418. |
| PMID 15286807 |
| Foxp1 regulates cardiac outflow tract, endocardial cushion morphogenesis and myocyte proliferation and maturation. |
| Wang B, Weidenfeld J, Lu MM, Maika S, Kuziel WA, Morrisey EE, Tucker PW |
| Development (Cambridge, England). 2004 ; 131 (18) : 4477-4487. |
| PMID 15342473 |
| Expression of the FOXP1 transcription factor is strongly associated with inferior survival in patients with diffuse large B-cell lymphoma. |
| Banham AH, Connors JM, Brown PJ, Cordell JL, Ott G, Sreenivasan G, Farinha P, Horsman DE, Gascoyne RD |
| Clinical cancer research : an official journal of the American Association for Cancer Research. 2005 ; 11 (3) : 1065-1072. |
| PMID 15709173 |
| The FOXP1 transcription factor is expressed in the majority of follicular lymphomas but is rarely expressed in classical and lymphocyte predominant Hodgkin's lymphoma. |
| Brown P, Marafioti T, Kusec R, Banham AH |
| Journal of molecular histology. 2005 ; 36 (4) : 249-256. |
| PMID 16200457 |
| T(3;14)(p14.1;q32) involving IGH and FOXP1 is a novel recurrent chromosomal aberration in MALT lymphoma. |
| Streubel B, Vinatzer U, Lamprecht A, Raderer M, Chott A |
| Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2005 ; 19 (4) : 652-658. |
| PMID 15703784 |
| FOXP1, a gene highly expressed in a subset of diffuse large B-cell lymphoma, is recurrently targeted by genomic aberrations. |
| Wlodarska I, Veyt E, De Paepe P, Vandenberghe P, Nooijen P, Theate I, Michaux L, Sagaert X, Marynen P, Hagemeijer A, De Wolf-Peeters C |
| Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2005 ; 19 (8) : 1299-1305. |
| PMID 15944719 |
| t(3;14)(p14;q32) results in aberrant expression of FOXP1 in a case of diffuse large B-cell lymphoma. |
| Fenton JA, Schuuring E, Barrans SL, Banham AH, Rollinson SJ, Morgan GJ, Jack AS, van Krieken JH, Kluin PM |
| Genes, chromosomes & cancer. 2006 ; 45 (2) : 164-168. |
| PMID 16252263 |
| 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. |
| Giatromanolaki A, Koukourakis MI, Sivridis E, Gatter KC, Harris AL, Banham AH |
| Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc. 2006 ; 19 (1) : 9-16. |
| PMID 16258506 |
| Genetic rearrangement of FOXP1 is predominantly detected in a subset of diffuse large B-cell lymphomas with extranodal presentation. |
| Haralambieva E, Adam P, Ventura R, Katzenberger T, Kalla J, Hller S, Hartmann M, Rosenwald A, Greiner A, Muller-Hermelink HK, Banham AH, Ott G |
| Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2006 ; 20 (7) : 1300-1303. |
| PMID 16673020 |
| Foxp1 is an essential transcriptional regulator of B cell development. |
| Hu H, Wang B, Borde M, Nardone J, Maika S, Allred L, Tucker PW, Rao A |
| Nature immunology. 2006 ; 7 (8) : 819-826. |
| PMID 16819554 |
| Forkhead box protein P1 expression in mucosa-associated lymphoid tissue lymphomas predicts poor prognosis and transformation to diffuse large B-cell lymphoma. |
| Sagaert X, de Paepe P, Libbrecht L, Vanhentenrijk V, Verhoef G, Thomas J, Wlodarska I, De Wolf-Peeters C |
| Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2006 ; 24 (16) : 2490-2497. |
| PMID 16636337 |
| Reduced expressions of Foxp1 and Rassf1a genes in lung adenocarcinomas induced by N-nitrosobis(2-hydroxypropyl)amine in rats. |
| Shimizu K, Kato A, Hinotsume D, Shigemura M, Hanaoka M, Shimoichi Y, Honoki K, Tsujiuchi T |
| Cancer letters. 2006 ; 236 (2) : 186-190. |
| PMID 16023287 |
| Expression of the forkhead transcription factor FOXP1 is associated both with hypoxia inducible factors (HIFs) and the androgen receptor in prostate cancer but is not directly regulated by androgens or hypoxia. |
| Banham AH, Boddy J, Launchbury R, Han C, Turley H, Malone PR, Harris AL, Fox SB |
| The Prostate. 2007 ; 67 (10) : 1091-1098. |
| PMID 17477366 |
| FOXP1: a potential therapeutic target in cancer. |
| Koon HB, Ippolito GC, Banham AH, Tucker PW |
| Expert opinion on therapeutic targets. 2007 ; 11 (7) : 955-965. |
| PMID 17614763 |
| Genome-wide analysis of genetic alterations in acute lymphoblastic leukaemia. |
| Mullighan CG, Goorha S, Radtke I, Miller CB, Coustan-Smith E, Dalton JD, Girtman K, Mathew S, Ma J, Pounds SB, Su X, Pui CH, Relling MV, Evans WE, Shurtleff SA, Downing JR |
| Nature. 2007 ; 446 (7137) : 758-764. |
| PMID 17344859 |
| REVIEW articles | automatic search in PubMed |
| Last year publications | automatic search in PubMed |
| Contributor(s) |
| Written | 08-2007 | Iwona Wlodarska |
| Department of Human Genetics, Catholic University Leuven, Leuven, Belgium |
| Citation |
| This paper should be referenced as such : |
| Wlodarska I . FOXP1 (Forkhead box P1). Atlas Genet Cytogenet Oncol Haematol. August 2007 . URL : http://AtlasGeneticsOncology.org/Genes/FOXP1ID40632ch3p14.html |
| © Atlas of Genetics and Cytogenetics in Oncology and Haematology | indexed on : Wed Jul 2 08:23:42 2008 |
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