Atlas of Genetics and Cytogenetics in Oncology and Haematology
NKX2-2 (NK2 homeobox 2)
| Identity |
| Other names | NKX2.2 |
| NKX2B | |
| Hugo | NKX2-2 |
| Location | 20p11.22 |
| DNA/RNA |
| Description | Start- 21,439,648 base pairs from p arm terminus; End- 21,442,699 base pairs from p arm terminus; Size- 3,051 bases; Orientation- minus strand |
| Protein |
 | |
| Schematic of NKX2-2 functional domains. The positions of the transcriptional repressor domain (TN), the homeodomain (HD), the NK2-specific domain (SD), and the transcriptional activation domain (TAD) are shown. | |
| Description | 273 amino acids; 30133 Da. NKX2-2 is a member of the NK2 family of homeobox transcription factors. It has known roles in the development of the CNS as well as pancreatic beta cell differentiation. In the CNS NKX2-2 is known to be activated by SHH signaling which is important for its initial role in ventral patterning. NKX2-2 expression has additionally been shown to be critical for the differentiation of oligodendrocytes, and in fact necessary for this process to occur. In both instances, NKX2-2 mediated transcripitional repression is both necessary and sufficient for these processes to occur. Regulation of NKX2-2 expression in the pancreas is less well understood. NKX2-2 knock-out mice die soon after birth from diabetic complications as a result of a lack of fully differentiated pancreatic beta cells. While NKX2-2 mediated transcriptional repression has been demonstrated to be necessary and sufficient for its role in ß-cell differentiation, it remains unclear whether NKX2-2 mediated transcriptional activation is important for NKX2-2 function in adult ß-cells. |
| Expression | V3 neural progenitors; oligodendrocyte precursor cells; precursor and adult pancreatic beta cells. |
| Localisation | Nuclear |
| Function | NKX2-2 is a transcription factor |
| Homology | NKX2-2 shares homology with other members of the NK2 family of transcription factors most notably in the TN transcriptional repression, DNA binding homeodomain, and specific domain regions. |
| Implicated in |
| Entity | Ewing's sarcoma |
| Prognosis | Roughly 50% survival at 5 years for Ewing's sarcoma. |
| Cytogenetics | Ewing's sarcoma cells harbor the characteristic translocation t(11;22)(q24;q12) in roughly 90% of cases. |
| Hybrid/Mutated Gene | t(11;22)(q24;q12) fuses the 5' region of the EWSR1 gene on chromosome 22 with the 3' portion of the FLI-1 gene on chromosome 11. |
| Abnormal Protein | The translocation fusion product is termed EWS/FLI. |
 | |
| Schematic diagram of wild-type EWS, wild-type FLI, and the EWS/FLI fusion transcripts. | |
| Oncogenesis | NKX2-2 is up-regulated in Ewing's sarcoma by the EWS/FLI translocation protein product. NKX2.2 expression is necessary for the oncogenic phenotype of Ewing's sarcoma cells. |
| External links |
| Bibliography |
| Gene fusion with an ETS DNA-binding domain caused by chromosome translocation in human tumours. |
| Delattre O, Zucman J, Plougastel B, Desmaze C, Melot T, Peter M, Kovar H, Joubert I, de Jong P, Rouleau G |
| Nature. 1992 ; 359 (6391) : 162-165. |
| PMID 1522903 |
| Ewing sarcoma 11;22 translocation produces a chimeric transcription factor that requires the DNA-binding domain encoded by FLI1 for transformation. |
| May WA, Gishizky ML, Lessnick SL, Lunsford LB, Lewis BC, Delattre O, Zucman J, Thomas G, Denny CT |
| Proceedings of the National Academy of Sciences of the United States of America. 1993 ; 90 (12) : 5752-5756. |
| PMID 8516324 |
| Mice lacking the homeodomain transcription factor Nkx2.2 have diabetes due to arrested differentiation of pancreatic beta cells. |
| Sussel L, Kalamaras J, Hartigan-O'Connor DJ, Meneses JJ, Pedersen RA, Rubenstein JL, German MS |
| Development (Cambridge, England). 1998 ; 125 (12) : 2213-2221. |
| PMID 9584121 |
| Homeobox gene Nkx2.2 and specification of neuronal identity by graded Sonic hedgehog signalling. |
| Briscoe J, Sussel L, Serup P, Hartigan-O'Connor D, Jessell TM, Rubenstein JL, Ericson J |
| Nature. 1999 ; 398 (6728) : 622-627. |
| PMID 10217145 |
| Intramolecular control of transcriptional activity by the NK2-specific domain in NK-2 homeodomain proteins. |
| Watada H, Mirmira RG, Kalamaras J, German MS |
| Proceedings of the National Academy of Sciences of the United States of America. 2000 ; 97 (17) : 9443-9448. |
| PMID 10944215 |
| Groucho-mediated transcriptional repression establishes progenitor cell pattern and neuronal fate in the ventral neural tube. |
| Muhr J, Andersson E, Persson M, Jessell TM, Ericson J |
| Cell. 2001 ; 104 (6) : 861-873. |
| PMID 11290324 |
| Stage-specific expression of myelin basic protein in oligodendrocytes involves Nkx2.2-mediated repression that is relieved by the Sp1 transcription factor. |
| Wei Q, Miskimins WK, Miskimins R |
| The Journal of biological chemistry. 2005 ; 280 (16) : 16284-16294. |
| PMID 15695521 |
| Identification of target genes in their native cellular context: an analysis of EWS/FLI in Ewing's sarcoma. |
| Owen LA, Lessnick SL |
| Cell cycle (Georgetown, Tex.). 2006 ; 5 (18) : 2049-2053. |
| PMID 16969112 |
| Expression profiling of EWS/FLI identifies NKX2.2 as a critical target gene in Ewing's sarcoma. |
| Smith R, Owen LA, Trem DJ, Wong JS, Whangbo JS, Golub TR, Lessnick SL |
| Cancer cell. 2006 ; 9 (5) : 405-416. |
| PMID 16697960 |
| Nkx2.2-repressor activity is sufficient to specify alpha-cells and a small number of beta-cells in the pancreatic islet. |
| Doyle MJ, Loomis ZL, Sussel L |
| Development (Cambridge, England). 2007 ; 134 (3) : 515-523. |
| PMID 17202186 |
| REVIEW articles | automatic search in PubMed |
| Last year publications | automatic search in PubMed |
| Contributor(s) |
| Written | 01-2008 | Stephen L Lessnick, Leah A Owen |
| Department of Oncological Sciences, University of Utah School of Medicine, Center for Children, Huntsman Cancer Institute, and Division of Pediatric Hematology/Oncology, University of Utah School of Medicine, Salt Lake City, Utah, USA |
| Citation |
| This paper should be referenced as such : |
| Lessnick SL, Owen LA . NKX2-2 (NK2 homeobox 2). Atlas Genet Cytogenet Oncol Haematol. January 2008 . URL : http://AtlasGeneticsOncology.org/Genes/NKX22ID44177ch20p11.html |
| © Atlas of Genetics and Cytogenetics in Oncology and Haematology | indexed on : Wed Jul 2 08:25:29 2008 |
For comments and suggestions or contributions, please contact us