SOX9
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| Location (UCSC) | Chr 17: 72.12 – 72.13 Mb | Chr 11: 112.67 – 112.68 Mb | |||||||
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Transcription factor SOX-9 is a protein that in humans is encoded by the SOX9 gene.[5][6]
Function
SOX-9 recognizes the sequence CCTTGAG along with other members of the
SOX-9 also plays a pivotal role in male sexual development; by working with Sf1, SOX-9 can produce AMH in
Sox9, also known as SRY-Box Transcription Factor 9, is an important gene is sex determination. The SOX family of genes are all transcription factors for the Y chromosomal sex-determining factor SRY. The SRY gene encodes the SOX transcription factor while it upregulates Sox9. Sox9 then activates Fgf9, Fibroblast growth factor 9, which is another integral transcription factor in the formation of the male gonads. Fgf9 up-regulates Sox9 in a positive feedforward cascade, this causes the differentiation of sertoli cells leading to the formation of the testis.[13]
SOX-9 is a target of the
In adult articular chondrocytes,
Clinical significance
Mutations lead to the skeletal malformation syndrome
SOX9 sits in a
The SOX9 protein has been implicated in both initiation and progression of multiple solid tumors.[19] Its role as a master regulator of morphogenesis during human development makes it an ideal candidate for perturbation in malignant tissues. Specifically, SOX9 appears to induce invasiveness and therapy-resistance in prostate,[20] colorectal,[21] breast[22] and other cancers, and therefore promotes lethal metastasis.[23] Many of these oncogenic effects of SOX9 appear dose-dependent.[24][20][19]
SOX9 localization and dynamics
SOX9 is mostly localizatied in the nucleus and it is highly mobile. Studies in chondrocyte cell line has revealed nearly 50% of SOX9 is bound to DNA and it is directly regulated by external factors. Its half-time of residence on DNA is ~14 seconds.[25]
Role in Sexual Differentiation
SOX9 helps channel SRY activation in sexual differentiation.
Interactions
SOX9 has been shown to
Knock out models
Loss of function mutations with Sox9 can lead to campomelic dysplasia(CD), due to mutations affecting protein functions and translocations that disrupt gene expression. There have been Sox9 knockout mice that have shown improved stroke recovery, especially when inhibiting inhibitors of axonal sprouting such as NOGO and chondroitin sulfate proteoglycans (CSPGs). Sox9 ablation leads to decreased levels of CSPG, which increases tissue sparing and improved post-stroke neurological recovery. These Sox9 knockout mice promote reparative axonal sprouting, neuroprotection and recovery after stroke.[31]
See also
- SOX genes
Further reading
- Ninomiya S, Narahara K, Tsuji K, Yokoyama Y, Ito S, Seino Y (March 1995). "Acampomelic campomelic syndrome and sex reversal associated with de novo t(12;17) translocation". American Journal of Medical Genetics. 56 (1): 31–34. PMID 7747782.
- Lefebvre V, de Crombrugghe B (March 1998). "Toward understanding SOX9 function in chondrocyte differentiation". Matrix Biology. 16 (9): 529–540. PMID 9569122.
- Harley VR (2002). "The Molecular Action of Testis-Determining Factors SRY and SOX9". The Genetics and Biology of Sex Determination. Novartis Foundation Symposia. Vol. 244. pp. 57–66, discussion 66–7, 79–85, 253–7. PMID 11990798.
- Kwok C, Weller PA, Guioli S, Foster JW, Mansour S, Zuffardi O, et al. (November 1995). "Mutations in SOX9, the gene responsible for Campomelic dysplasia and autosomal sex reversal". American Journal of Human Genetics. 57 (5): 1028–1036. PMID 7485151.
- Foster JW, Dominguez-Steglich MA, Guioli S, Kwok C, Weller PA, Stevanović M, et al. (December 1994). "Campomelic dysplasia and autosomal sex reversal caused by mutations in an SRY-related gene". Nature. 372 (6506): 525–530. S2CID 1472426.
- Wagner T, Wirth J, Meyer J, Zabel B, Held M, Zimmer J, et al. (December 1994). "Autosomal sex reversal and campomelic dysplasia are caused by mutations in and around the SRY-related gene SOX9". Cell. 79 (6): 1111–1120. S2CID 24982682.
- Südbeck P, Schmitz ML, Baeuerle PA, Scherer G (June 1996). "Sex reversal by loss of the C-terminal transactivation domain of human SOX9". Nature Genetics. 13 (2): 230–232. S2CID 22617889.
- Cameron FJ, Hageman RM, Cooke-Yarborough C, Kwok C, Goodwin LL, Sillence DO, et al. (October 1996). "A novel germ line mutation in SOX9 causes familial campomelic dysplasia and sex reversal". Human Molecular Genetics. 5 (10): 1625–1630. PMID 8894698.
- Meyer J, Südbeck P, Held M, Wagner T, Schmitz ML, Bricarelli FD, et al. (January 1997). "Mutational analysis of the SOX9 gene in campomelic dysplasia and autosomal sex reversal: lack of genotype/phenotype correlations". Human Molecular Genetics. 6 (1): 91–98. PMID 9002675.
- Cameron FJ, Sinclair AH (1997). "Mutations in SRY and SOX9: testis-determining genes". Human Mutation. 9 (5): 388–395. S2CID 45387678.
- Wunderle VM, Critcher R, Hastie N, Goodfellow PN, Schedl A (September 1998). "Deletion of long-range regulatory elements upstream of SOX9 causes campomelic dysplasia". Proceedings of the National Academy of Sciences of the United States of America. 95 (18): 10649–10654. PMID 9724758.
- De Santa Barbara P, Bonneaud N, Boizet B, Desclozeaux M, Moniot B, Sudbeck P, et al. (November 1998). "Direct interaction of SRY-related protein SOX9 and steroidogenic factor 1 regulates transcription of the human anti-Müllerian hormone gene". Molecular and Cellular Biology. 18 (11): 6653–6665. PMID 9774680.
- McDowall S, Argentaro A, Ranganathan S, Weller P, Mertin S, Mansour S, et al. (August 1999). "Functional and structural studies of wild type SOX9 and mutations causing campomelic dysplasia". The Journal of Biological Chemistry. 274 (34): 24023–24030. PMID 10446171.
- Huang W, Zhou X, Lefebvre V, de Crombrugghe B (June 2000). "Phosphorylation of SOX9 by cyclic AMP-dependent protein kinase A enhances SOX9's ability to transactivate a Col2a1 chondrocyte-specific enhancer". Molecular and Cellular Biology. 20 (11): 4149–4158. PMID 10805756.
- Thong MK, Scherer G, Kozlowski K, Haan E, Morris L (August 2000). "Acampomelic campomelic dysplasia with SOX9 mutation". American Journal of Medical Genetics. 93 (5): 421–425. PMID 10951468.
- Ninomiya S, Yokoyama Y, Teraoka M, Mori R, Inoue C, Yamashita S, et al. (September 2000). "A novel mutation (296 del G) of the SOX90 gene in a patient with campomelic syndrome and sex reversal". Clinical Genetics. 58 (3): 224–227. S2CID 28618271.
- Preiss S, Argentaro A, Clayton A, John A, Jans DA, Ogata T, et al. (July 2001). "Compound effects of point mutations causing campomelic dysplasia/autosomal sex reversal upon SOX9 structure, nuclear transport, DNA binding, and transcriptional activation". The Journal of Biological Chemistry. 276 (30): 27864–27872. PMID 11323423.
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000125398 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000000567 – 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.
- S2CID 12263655.
- ^ a b c "Entrez Gene: SOX9 SRY (sex determining region Y)-box 9 (campomelic dysplasia, autosomal sex-reversal)".
- ISBN 9780808924500.
- ^ PMID 9774680.
- ^ PMID 19429785.
- ^ PMID 16700629.
- ^ PMID 15944188.
- PMID 30392800.
- PMID 28045957.
- ^ Place E, Manning E, Kim DW, Kinjo A, Nakamura G and Ohyama K (2022) SHH and Notch regulate SOX9+ progenitors to govern arcuate POMC neurogenesis. Front. Neurosci. 16:855288. doi: 10.3389/fnins.2022.855288
- ^ Vogel, Julia K.; Wegner, Michael PhD,*. Sox9 in the developing central nervous system: a jack of all trades?. Neural Regeneration Research 16(4):p 676-677, April 2021. | DOI: 10.4103/1673-5374.295327
- PMID 33043724.
- ^ PMID 21331089.
- S2CID 29933548.
- ^ PMID 25685828.
- ^ PMID 31919137.
- PMID 28988015.
- PMID 30914279.
- PMID 31057614.
- PMID 30642390.
- PMID 30465885.
- PMID 10602113.
- PMID 28045957.
- PMID 12136106.
- PMID 12381733.
- PMID 37488435.
- PMID 29425963.
External links
- SOX9+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- SOX9 human gene location in the UCSC Genome Browser.
- SOX9 human gene details in the UCSC Genome Browser.
- Overview of all the structural information available in the PDB for UniProt: P48436 (Human Transcription factor SOX-9) at the PDBe-KB.
- Overview of all the structural information available in the PDB for UniProt: Q04887 (Mouse Transcription factor SOX-9) at the PDBe-KB.
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This article incorporates text from the United States National Library of Medicine, which is in the public domain.