Tenascin C
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| Location (UCSC) | Chr 9: 115.02 – 115.12 Mb | Chr 4: 63.88 – 63.97 Mb | |||||||
| PubMed search | [3] | [4] | |||||||
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Tenascin C (TN-C) is a glycoprotein that in humans is encoded by the TNC gene.[5][6] It is expressed in the extracellular matrix of various tissues during development, disease or injury, and in restricted neurogenic areas of the central nervous system.[7][8] Tenascin-C is the founding member of the tenascin protein family. In the embryo it is made by migrating cells like the neural crest; it is also abundant in developing tendons, bone and cartilage.
Gene and expression
The human tenascin C gene, TN-C, is located on
Expression of TN-C changes from development to adulthood. TN-C is highly expressed during
The regulation of TN-C is induced or repressed by a number of different factors that are expressed during embryonic tissue, as well as developed tissues during remodeling, injured, or neoplastic.
In the developing central nervous system, TN-C is involved in regulating the proliferation of both
Structure
Tenascin C is an
Interactions
Tenascin-C has been shown to
TN-C also interacts with one or more TN-C receptors on cells which activate and repress the same signal transduction pathway. An example of this interaction is the adhesion of SW80 carcinoma cells to the third FN-III repeat of TN-C via the αvβ3 integrin receptor leads to cell spreading, phosphorylation of focal adhesion kinase, paxillin and ERK2 MAPK, and proliferation.[18] In contrast, when these same cells use either α9β1 or αvβ6 integrins to adhere to the same third FN type III repeat, cell spreading is attenuated and activation of these signaling mediators and cell growth is suppressed or fails to occur.
Function
Tenascin C is a very diverse protein that can produce different functions within the same cell type. These myriad functions are accomplished through alternative splicing of mRNA as well as the temporal activation of signal transduction pathways and/or target genes at different stages of growth or differentiation.[12] TN-C is classified as an adhesion-modulating protein, because it has been found to inhibit cellular adhesion to fibronectin.[10]
Much of the functional studies are inferred from various TN-C knockout mice models. TN-C clearly plays a role in cell signaling as evidenced by its ability to be induced during events such as trauma, inflammation, or cancer development. Also, TN-C is important in regulating cell proliferation and migration, especially during developmental differentiation and wound healing.[19]
Clinical significance
Tenascin C continues to be researched as a potential biomarker for a number of diseases such as myocarditis[20] and different forms of cancer. The numerous involvements with cellular functioning and signaling make TN-C a popular protein to study in developing new therapies and detection methods. Recent work has shown that TN-C inhibits HIV infection in immune cells by binding to a
Role in cancer
Tenascin C is implicated in a number of different cancers such as
See also
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000041982 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000028364 – 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.
- PMID 1704365.
- PMID 1707164.
- PMID 21818551.
- ^ PMID 22740833.
- ^ PMID 1719530.
- ^ PMID 15094113.
- S2CID 44707905.
- ^ PMID 11102748.
- S2CID 45283679.
- PMID 1696875.
- PMID 7499434.
- PMID 9314546.
- PMID 7519905.
- PMID 8798654.
- PMID 7694605.
- S2CID 7043057.
- PMID 24145401.
- PMID 30976088.
- PMID 10762653.
- S2CID 46848271.
- PMID 15333651.
- ^ S2CID 34313902.
- PMID 14676325.
- PMID 16632194.
Further reading
- Imanaka-Yoshida K, Hiroe M, Yoshida T (2004). "Interaction between cell and extracellular matrix in heart disease: multiple roles of tenascin-C in tissue remodeling". Histol. Histopathol. 19 (2): 517–25. PMID 15024713.
- Leahy DJ, Hendrickson WA, Aukhil I, Erickson HP (1992). "Structure of a fibronectin type III domain from tenascin phased by MAD analysis of the selenomethionyl protein". Science. 258 (5084): 987–91. PMID 1279805.
- White DM, Mikol DD, Espinosa R, et al. (1992). "Structure and chromosomal localization of the human gene for a brain form of prostaglandin D2 synthase". J. Biol. Chem. 267 (32): 23202–8. PMID 1385416.
- Gulcher JR, Nies DE, Marton LS, Stefansson K (1989). "An alternatively spliced region of the human hexabrachion contains a repeat of potential N-glycosylation sites". Proc. Natl. Acad. Sci. U.S.A. 86 (5): 1588–92. PMID 2466295.
- Yokosaki Y, Palmer EL, Prieto AL, et al. (1994). "The integrin alpha 9 beta 1 mediates cell attachment to a non-RGD site in the third fibronectin type III repeat of tenascin". J. Biol. Chem. 269 (43): 26691–6. PMID 7523411.
- Glumoff V, Savontaus M, Vehanen J, Vuorio E (1994). "Analysis of aggrecan and tenascin gene expression in mouse skeletal tissues by northern and in situ hybridization using species specific cDNA probes". Biochim. Biophys. Acta. 1219 (3): 613–22. PMID 7524681.
- Gherzi R, Carnemolla B, Siri A, et al. (1995). "Human tenascin gene. Structure of the 5'-region, identification, and characterization of the transcription regulatory sequences". J. Biol. Chem. 270 (7): 3429–34. PMID 7531707.
- Weinacker A, Ferrando R, Elliott M, et al. (1995). "Distribution of integrins alpha v beta 6 and alpha 9 beta 1 and their known ligands, fibronectin and tenascin, in human airways". Am. J. Respir. Cell Mol. Biol. 12 (5): 547–56. PMID 7537970.
- Schnapp LM, Hatch N, Ramos DM, et al. (1995). "The human integrin alpha 8 beta 1 functions as a receptor for tenascin, fibronectin, and vitronectin". J. Biol. Chem. 270 (39): 23196–202. PMID 7559467.
- Sriramarao P, Mendler M, Bourdon MA (1993). "Endothelial cell attachment and spreading on human tenascin is mediated by alpha 2 beta 1 and alpha v beta 3 integrins". J. Cell Sci. 105 (4): 1001–12. PMID 7693733.
- Prieto AL, Edelman GM, Crossin KL (1993). "Multiple integrins mediate cell attachment to cytotactin/tenascin". Proc. Natl. Acad. Sci. U.S.A. 90 (21): 10154–8. PMID 7694284.
- Zagzag D, Friedlander DR, Dosik J, et al. (1996). "Tenascin-C expression by angiogenic vessels in human astrocytomas and by human brain endothelial cells in vitro". Cancer Res. 56 (1): 182–9. PMID 8548761.
- Burg MA, Tillet E, Timpl R, Stallcup WB (1996). "Binding of the NG2 proteoglycan to type VI collagen and other extracellular matrix molecules". J. Biol. Chem. 271 (42): 26110–6. PMID 8824254.
- Rauch U, Clement A, Retzler C, et al. (1997). "Mapping of a defined neurocan binding site to distinct domains of tenascin-C". J. Biol. Chem. 272 (43): 26905–12. PMID 9341124.
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