NK2 homeobox 1
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| Location (UCSC) | Chr 14: 36.52 – 36.52 Mb | Chr 12: 56.58 – 56.58 Mb | |||||||
| PubMed search | [3] | [4] | |||||||
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NK2 homeobox 1 (NKX2-1), also known as thyroid transcription factor 1 (TTF-1), is a protein which in humans is encoded by the NKX2-1 gene.[5][6]
Function
Thyroid transcription factor-1 (TTF-1) is a
NKX2.1 is key to the fetal development of lung structures. The dorsal-ventral pattern of NKX2.1 expression forms the ventral boundary in the anterior foregut. NKX2.1 is expressed only in select cells in the ventral wall of the anterior foregut, and is not expressed in the dorsal wall, where the esophagus will emerge from. NKX2.1 knockout in mice results in the development of a shortened trachea which is fused to the esophagus, with the bronchi directly connecting this shared tube to the lungs. This resembles a complete tracheoesophageal fistula, which is a rare congenital condition in humans. Furthermore, distal lung structures do not develop in these knockout mice. Branching of the lungs in these mice did not occur past the main-stem bronchi, resulting in lungs that were smaller in size by about 50% compared to the wild-type mice. The epithelial lining of these distal structures did not show evidence of differentiation into specialized cells. This lining is composed of columnar epithelial cells and scattered ciliated epithelial cells.[8] The proximal epithelium of the lungs showed normal differentiation, indicating that proximal differentiation is independent of NKX2.1. NKX2.1 is initially expressed in the entire epithelium, but is suppressed in a proximal-distal pattern as the lung continues to develop.[9]
Clinical significance
TTF-1 positive cells are found in the lung as
For
It has been observed that a loss of Nkx2-1 allows for deregulation of transcription factors
However others have found that TTF-1 staining is often positive in pulmonary adenocarcinomas, large cell carcinomas, small-cell lung carcinomas, neuroendocrine tumors other than small-cell lung carcinomas and extrapulmonary small-cell carcinomas.[16]
It is also positive in thyroid cancers and is used for monitoring for metastasis and recurrence.[17]
Interactions
NK2 homeobox 1 has been shown to
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000136352 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000001496 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Entrez Gene: NKX2-1".
- PMID 1976511.
- PMID 23259454.
- PMID 10208743.
- PMID 10706142.
- PMID 12562233.
- PMID 17925434.
- PMID 17616654.
- PMID 17982442.
- PMID 18212743.
- PMID 23523371.
- PMID 16680154.
- PMID 11463576.
- PMID 9988700.
- PMID 12441357.
Further reading
- Lau SK, Luthringer DJ, Eisen RN (June 2002). "Thyroid transcription factor-1: a review". Applied Immunohistochemistry & Molecular Morphology. 10 (2): 97–102. PMID 12051643.
- Guazzi S, Price M, De Felice M, Damante G, Mattei MG, Di Lauro R (November 1990). "Thyroid nuclear factor 1 (TTF-1) contains a homeodomain and displays a novel DNA binding specificity". The EMBO Journal. 9 (11): 3631–9. PMID 1976511.
- Oguchi H, Pan YT, Kimura S (April 1995). "The complete nucleotide sequence of the mouse thyroid-specific enhancer-binding protein (T/EBP) gene: extensive identity of the deduced amino acid sequence with the human protein". Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression. 1261 (2): 304–6. PMID 7711079.
- Saiardi A, Tassi V, De Filippis V, Civitareale D (April 1995). "Cloning and sequence analysis of human thyroid transcription factor 1". Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression. 1261 (2): 307–10. PMID 7711080.
- Ikeda K, Clark JC, Shaw-White JR, Stahlman MT, Boutell CJ, Whitsett JA (April 1995). "Gene structure and expression of human thyroid transcription factor-1 in respiratory epithelial cells". The Journal of Biological Chemistry. 270 (14): 8108–14. PMID 7713914.
- Bonaldo MF, Lennon G, Soares MB (September 1996). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Research. 6 (9): 791–806. PMID 8889548.
- Ghaffari M, Zeng X, Whitsett JA, Yan C (December 1997). "Nuclear localization domain of thyroid transcription factor-1 in respiratory epithelial cells". The Biochemical Journal. 328 ( Pt 3) (3): 757–61. PMID 9396717.
- Hamdan H, Liu H, Li C, Jones C, Lee M, deLemos R, Minoo P (March 1998). "Structure of the human Nkx2.1 gene". Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression. 1396 (3): 336–48. PMID 9545595.
- Perrone L, Tell G, Di Lauro R (February 1999). "Calreticulin enhances the transcriptional activity of thyroid transcription factor-1 by binding to its homeodomain". The Journal of Biological Chemistry. 274 (8): 4640–5. PMID 9988700.
- Naltner A, Ghaffari M, Whitsett JA, Yan C (January 2000). "Retinoic acid stimulation of the human surfactant protein B promoter is thyroid transcription factor 1 site-dependent". The Journal of Biological Chemistry. 275 (1): 56–62. PMID 10617585.
- Missero C, Pirro MT, Di Lauro R (April 2000). "Multiple ras downstream pathways mediate functional repression of the homeobox gene product TTF-1". Molecular and Cellular Biology. 20 (8): 2783–93. PMID 10733581.
- Naltner A, Wert S, Whitsett JA, Yan C (December 2000). "Temporal/spatial expression of nuclear receptor coactivators in the mouse lung". American Journal of Physiology. Lung Cellular and Molecular Physiology. 279 (6): L1066-74. S2CID 27872061.
- Yan C, Naltner A, Conkright J, Ghaffari M (June 2001). "Protein-protein interaction of retinoic acid receptor alpha and thyroid transcription factor-1 in respiratory epithelial cells". The Journal of Biological Chemistry. 276 (24): 21686–91. PMID 11274148.
- Missero C, Pirro MT, Simeone S, Pischetola M, Di Lauro R (September 2001). "The DNA glycosylase T:G mismatch-specific thymine DNA glycosylase represses thyroid transcription factor-1-activated transcription". The Journal of Biological Chemistry. 276 (36): 33569–75. PMID 11438542.
- Yi M, Tong GX, Murry B, Mendelson CR (January 2002). "Role of CBP/p300 and SRC-1 in transcriptional regulation of the pulmonary surfactant protein-A (SP-A) gene by thyroid transcription factor-1 (TTF-1)". The Journal of Biological Chemistry. 277 (4): 2997–3005. PMID 11713256.
- Liu C, Glasser SW, Wan H, Whitsett JA (February 2002). "GATA-6 and thyroid transcription factor-1 directly interact and regulate surfactant protein-C gene expression". The Journal of Biological Chemistry. 277 (6): 4519–25. PMID 11733512.
- Ng WK, Chow JC, Ng PK (February 2002). "Thyroid transcription factor-1 is highly sensitive and specific in differentiating metastatic pulmonary from extrapulmonary adenocarcinoma in effusion fluid cytology specimens". Cancer. 96 (1): 43–8. S2CID 23626036.
- Pohlenz J, Dumitrescu A, Zundel D, Martiné U, Schönberger W, Koo E, et al. (February 2002). "Partial deficiency of thyroid transcription factor 1 produces predominantly neurological defects in humans and mice". The Journal of Clinical Investigation. 109 (4): 469–73. PMID 11854318.
- Krude H, Schütz B, Biebermann H, von Moers A, Schnabel D, Neitzel H, et al. (February 2002). "Choreoathetosis, hypothyroidism, and pulmonary alterations due to human NKX2-1 haploinsufficiency". The Journal of Clinical Investigation. 109 (4): 475–80. PMID 11854319.
- Miccadei S, De Leo R, Zammarchi E, Natali PG, Civitareale D (April 2002). "The synergistic activity of thyroid transcription factor 1 and Pax 8 relies on the promoter/enhancer interplay". Molecular Endocrinology. 16 (4): 837–46. PMID 11923479.
External links
- TITF1+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
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This article incorporates text from the United States National Library of Medicine, which is in the public domain.