SOX2
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| Location (UCSC) | Chr 3: 181.71 – 181.71 Mb | Chr 3: 34.7 – 34.71 Mb | |||||||
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SRY (sex determining region Y)-box 2, also known as SOX2, is a
Sox2 is a member of the Sox
Sox2 holds great promise in research involving induced pluripotency, an emerging and very promising field of regenerative medicine.[6]
Function
Stem cell pluripotency
LIF (Leukemia inhibitory factor) signaling, which maintains pluripotency in mouse embryonic stem cells, activates Sox2 downstream of the JAK-STAT signaling pathway and subsequent activation of Klf4 (a member of the family of Kruppel-like factors). Oct-4, Sox2 and Nanog positively regulate transcription of all pluripotency circuitry proteins in the LIF pathway.[7]
In an experiment involving mouse embryonic stem cells, it was discovered that Sox2 in conjunction with Oct4,
Loss of pluripotency is regulated by hypermethylation of some Sox2 and Oct4 binding sites in male germ cells[12] and post-transcriptional suppression of Sox2 by miR134.[13]
Varying levels of Sox2 affect embryonic stem cells' fate of differentiation. Sox2 inhibits differentiation into the mesendoderm germ layer and promotes differentiation into neural ectoderm germ layer.[14] Npm1/Sox2 complexes are sustained when differentiation is induced along the ectodermal lineage, emphasizing an important functional role for Sox2 in ectodermal differentiation.[8] The loss of Sox2 has also been shown to affect naïve pluripotency, with Sox2-depleted mouse embryonic cells becoming able to differentiate into extraembryonic trophoblast.[15]
Deficiency of Sox2 in mice has been shown to result in neural malformities and eventually fetal death, further underlining Sox2's vital role in embryonic development.[16]
Neural stem cells
In
Induced pluripotency is possible using adult neural stem cells, which express higher levels of Sox2 and c-Myc than embryonic stem cells. Therefore, only two exogenous factors, one of which is necessarily Oct4, are sufficient for inducing pluripotent cells from neural stem cells, lessening the complications and risks associated with introducing multiple factors to induce pluripotency.[21]
Eye deformities
Mutations in this gene have been linked with bilateral anophthalmia, a severe structural eye deformity.[22]
Cancer
In lung development, Sox2 controls the branching morphogenesis of the bronchial tree and differentiation of the epithelium of airways. Overexpression causes an increase in neuroendocrine, gastric/intestinal and basal cells.[23] Under normal conditions, Sox2 is critical for maintaining self-renewal and appropriate proportion of basal cells in adult tracheal epithelium. However, its overexpression gives rise to extensive epithelial hyperplasia and eventually carcinoma in both developing and adult mouse lungs.[24]
In
Sox2 expression is also found in high
The ectopic expression of SOX2 may be related to abnormal differentiation of colorectal cancer cells.[29]
Sox2 has been shown to be relevant in the development of Tamoxifen resistance in breast cancer.[30]
In Glioblastoma multiforme, Sox2 is a well-established stem cell transcription factor needed to induce and maintain stemness properties of glioblastoma cancer cells.[31][32]
Regulation by thyroid hormone
There are three
Hypothyroidism can arise from a multitude of causes, and is commonly remedied with hormone treatments such as the commonly used Levothyroxine.[34]
Interactions
SOX2 has been shown to
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000181449 - Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000074637 - 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.
- ^ a b "SOX2". NCBI.
- PMID 20016762.
- ^ S2CID 4382543.
- ^ PMID 21076177.
- ^ PMID 19542351.
- S2CID 24074525.
- S2CID 1565219.
- PMID 16859545.
- S2CID 4330178.
- PMID 21663792.
- PMID 33665571.
- S2CID 26059456.
- S2CID 17162323.
- S2CID 53569740.
- PMID 18371391.
- PMID 16893969.
- S2CID 4318637.
- ^ "Entrez Gene: SOX2 SRY (sex determining region Y)-box 2".
- PMID 18374910.
- PMID 20548776.
- S2CID 19544093.
- PMID 24953650.
- PMID 20126410.
- PMID 23326489.
- S2CID 33410257.
- PMID 24178749.
- PMID 19896441.
- S2CID 19125999.
- ^ PMID 22560077.
- ^ Wisse B. Hypothyroidism: MedlinePlus Medical Encyclopedia. U.S National Library of Medicine. Retrieved 10 April 2014.
- PMID 12710953.
- PMID 16714766.
Further reading
- Kamachi Y, Uchikawa M, Kondoh H (April 2000). "Pairing SOX off: with partners in the regulation of embryonic development". Trends in Genetics. 16 (4): 182–187. PMID 10729834.
- Schepers GE, Teasdale RD, Koopman P (August 2002). "Twenty pairs of sox: extent, homology, and nomenclature of the mouse and human sox transcription factor gene families". Developmental Cell. 3 (2): 167–170. PMID 12194848.
- Hever AM, Williamson KA, van Heyningen V (June 2006). "Developmental malformations of the eye: the role of PAX6, SOX2 and OTX2". Clinical Genetics. 69 (6): 459–470. S2CID 5676139.
- Yuan H, Corbi N, Basilico C, Dailey L (November 1995). "Developmental-specific activity of the FGF-4 enhancer requires the synergistic action of Sox2 and Oct-3". Genes & Development. 9 (21): 2635–2645. PMID 7590241.
- Stevanovic M, Zuffardi O, Collignon J, Lovell-Badge R, Goodfellow P (October 1994). "The cDNA sequence and chromosomal location of the human SOX2 gene". Mammalian Genome. 5 (10): 640–642. S2CID 10841620.
- 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.
- Helland R, Berglund GI, Otlewski J, Apostoluk W, Andersen OA, Willassen NP, Smalås AO (January 1999). "High-resolution structures of three new trypsin-squash-inhibitor complexes: a detailed comparison with other trypsins and their complexes". Acta Crystallographica. Section D, Biological Crystallography. 55 (Pt 1): 139–148. PMID 10089404.
- Güre AO, Stockert E, Scanlan MJ, Keresztes RS, Jäger D, Altorki NK, et al. (April 2000). "Serological identification of embryonic neural proteins as highly immunogenic tumor antigens in small cell lung cancer". Proceedings of the National Academy of Sciences of the United States of America. 97 (8): 4198–4203. PMID 10760287.
- Ambrosetti DC, Schöler HR, Dailey L, Basilico C (July 2000). "Modulation of the activity of multiple transcriptional activation domains by the DNA binding domains mediates the synergistic action of Sox2 and Oct-3 on the fibroblast growth factor-4 enhancer". The Journal of Biological Chemistry. 275 (30): 23387–23397. PMID 10801796.
- Kamachi Y, Uchikawa M, Tanouchi A, Sekido R, Kondoh H (May 2001). "Pax6 and SOX2 form a co-DNA-binding partner complex that regulates initiation of lens development". Genes & Development. 15 (10): 1272–1286. PMID 11358870.
- Fantes J, Ragge NK, Lynch SA, McGill NI, Collin JR, Howard-Peebles PN, et al. (April 2003). "Mutations in SOX2 cause anophthalmia". Nature Genetics. 33 (4): 461–463. PMID 12612584.
- Wiebe MS, Nowling TK, Rizzino A (May 2003). "Identification of novel domains within Sox-2 and Sox-11 involved in autoinhibition of DNA binding and partnership specificity". The Journal of Biological Chemistry. 278 (20): 17901–17911. PMID 12637543.
- Aota S, Nakajima N, Sakamoto R, Watanabe S, Ibaraki N, Okazaki K (May 2003). "Pax6 autoregulation mediated by direct interaction of Pax6 protein with the head surface ectoderm-specific enhancer of the mouse Pax6 gene". Developmental Biology. 257 (1): 1–13. PMID 12710953.
- Schepers G, Wilson M, Wilhelm D, Koopman P (July 2003). "SOX8 is expressed during testis differentiation in mice and synergizes with SF1 to activate the Amh promoter in vitro". The Journal of Biological Chemistry. 278 (30): 28101–28108. PMID 12732652.
- Reményi A, Lins K, Nissen LJ, Reinbold R, Schöler HR, Wilmanns M (August 2003). "Crystal structure of a POU/HMG/DNA ternary complex suggests differential assembly of Oct4 and Sox2 on two enhancers". Genes & Development. 17 (16): 2048–2059. PMID 12923055.
- Williams DC, Cai M, Clore GM (January 2004). "Molecular basis for synergistic transcriptional activation by Oct1 and Sox2 revealed from the solution structure of the 42-kDa Oct1.Sox2.Hoxb1-DNA ternary transcription factor complex". The Journal of Biological Chemistry. 279 (2): 1449–1457. PMID 14559893.
- Tsukamoto T, Inada K, Tanaka H, Mizoshita T, Mihara M, Ushijima T, et al. (March 2004). "Down-regulation of a gastric transcription factor, Sox2, and ectopic expression of intestinal homeobox genes, Cdx1 and Cdx2: inverse correlation during progression from gastric/intestinal-mixed to complete intestinal metaplasia". Journal of Cancer Research and Clinical Oncology. 130 (3): 135–145. S2CID 19831132.
External links
- Young Lab- Core Transcriptional Regulatory Circuitry in Human Embryonic Stem Cells
- GeneReviews/NCBI/NIH/UW entry on SOX2-related eye disorders
- Generating iPS Cells from MEFS through Forced Expression of Sox-2, Oct-4, c-Myc, and Klf4 (Journal of Visualized Experiments)
- GeneReviews/NCBI/NIH/UW entry on Anophthalmia / Microphthalmia Overview
- Overview of all the structural information available in the PDB for UniProt: P48431 (Human Transcription factor SOX-2) at the PDBe-KB.
- Overview of all the structural information available in the PDB for UniProt: P48432 (Mouse Transcription factor SOX-2) at the PDBe-KB.
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