CST6 (gene)
Cystatin-M is a protein that in humans is encoded by the CST6 gene.[1][2][3]
The cystatin superfamily encompasses proteins that contain multiple cystatin-like sequences. Some of the members are active cysteine protease inhibitors, while others have lost or perhaps never acquired this inhibitory activity. There are three inhibitory families in the superfamily, including the type 1 cystatins (stefins), type 2 cystatins and the kininogens. The type 2 cystatin proteins are a class of cysteine proteinase inhibitors found in a variety of human fluids and secretions, where they appear to provide protective functions. This gene encodes a cystatin from the type 2 family, which is down-regulated in metastatic breast tumor cells as compared to primary tumor cells. Loss of expression is likely associated with the progression of a primary tumor to a metastatic phenotype.[3]
References
- ^ Stenman G, Astrom AK, Roijer E, Sotiropoulou G, Zhang M, Sager R (Jun 1997). "Assignment of a novel cysteine proteinase inhibitor (CST6) to 11q13 by fluorescence in situ hybridization". Cytogenet Cell Genet 76 (1-2): 45–6. doi:10.1159/000134512. PMID 9154125.
- ^ Ni J, Abrahamson M, Zhang M, Fernandez MA, Grubb A, Su J, Yu GL, Li Y, Parmelee D, Xing L, Coleman TA, Gentz S, Thotakura R, Nguyen N, Hesselberg M, Gentz R (May 1997). "Cystatin E is a novel human cysteine proteinase inhibitor with structural resemblance to family 2 cystatins". J Biol Chem 272 (16): 10853–8. doi:10.1074/jbc.272.16.10853. PMID 9099741.
- ^ a b "Entrez Gene: CST6 cystatin E/M". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1474.
External Links
- The MEROPS online database for peptidases and their inhibitors: I25.006
Further reading
- Brown WM, Dziegielewska KM (1997). "Friends and relations of the cystatin superfamily--new members and their evolution.". Protein Sci. 6 (1): 5–12. doi:10.1002/pro.5560060102. PMC 2143511. PMID 9007972. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2143511.
- Barka T, Asbell PA, van der Noen H, Prasad A (1991). "Cystatins in human tear fluid.". Curr. Eye Res. 10 (1): 25–34. doi:10.3109/02713689109007608. PMID 2029847.
- Saitoh E, Isemura S, Sanada K, et al. (1989). "Cystatin superfamily. Evidence that family II cystatin genes are evolutionarily related to family III cystatin genes.". Biol. Chem. Hoppe-Seyler. 369 Suppl: 191–7. PMID 3202964.
- Thiesse M, Millar SJ, Dickinson DP (1994). "The human type 2 cystatin gene family consists of eight to nine members, with at least seven genes clustered at a single locus on human chromosome 20.". DNA Cell Biol. 13 (2): 97–116. doi:10.1089/dna.1994.13.97. PMID 8179826.
- Sotiropoulou G, Anisowicz A, Sager R (1997). "Identification, cloning, and characterization of cystatin M, a novel cysteine proteinase inhibitor, down-regulated in breast cancer.". J. Biol. Chem. 272 (2): 903–10. doi:10.1074/jbc.272.2.903. PMID 8995380.
- Zeeuwen PL, Van Vlijmen-Willems IM, Jansen BJ, et al. (2001). "Cystatin M/E expression is restricted to differentiated epidermal keratinocytes and sweat glands: a new skin-specific proteinase inhibitor that is a target for cross-linking by transglutaminase.". J. Invest. Dermatol. 116 (5): 693–701. doi:10.1046/j.1523-1747.2001.01309.x. PMID 11348457.
- Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=139241.
- Zeeuwen PL, Dale BA, de Jongh GJ, et al. (2003). "The human cystatin M/E gene (CST6): exclusion candidate gene for harlequin ichthyosis.". J. Invest. Dermatol. 121 (1): 65–8. doi:10.1046/j.1523-1747.2003.12312.x. PMID 12839564.
- Shridhar R, Zhang J, Song J, et al. (2004). "Cystatin M suppresses the malignant phenotype of human MDA-MB-435S cells.". Oncogene 23 (12): 2206–15. doi:10.1038/sj.onc.1207340. PMID 14676833.
- Zhang J, Shridhar R, Dai Q, et al. (2004). "Cystatin m: a novel candidate tumor suppressor gene for breast cancer.". Cancer Res. 64 (19): 6957–64. doi:10.1158/0008-5472.CAN-04-0819. PMID 15466187.
- Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=528928.
- Song J, Jie C, Polk P, et al. (2006). "The candidate tumor suppressor CST6 alters the gene expression profile of human breast carcinoma cells: down-regulation of the potent mitogenic, motogenic, and angiogenic factor autotaxin.". Biochem. Biophys. Res. Commun. 340 (1): 175–82. doi:10.1016/j.bbrc.2005.11.171. PMID 16356477.
- Cheng T, Hitomi K, van Vlijmen-Willems IM, et al. (2006). "Cystatin M/E is a high affinity inhibitor of cathepsin V and cathepsin L by a reactive site that is distinct from the legumain-binding site. A novel clue for the role of cystatin M/E in epidermal cornification.". J. Biol. Chem. 281 (23): 15893–9. doi:10.1074/jbc.M600694200. PMID 16565075.
- Ai L, Kim WJ, Kim TY, et al. (2007). "Epigenetic silencing of the tumor suppressor cystatin M occurs during breast cancer progression.". Cancer Res. 66 (16): 7899–909. doi:10.1158/0008-5472.CAN-06-0576. PMID 16912163.
- Rivenbark AG, Jones WD, Coleman WB (2007). "DNA methylation-dependent silencing of CST6 in human breast cancer cell lines.". Lab. Invest. 86 (12): 1233–42. doi:10.1038/labinvest.3700485. PMID 17043665.
- Schagdarsurengin U, Pfeifer GP, Dammann R (2007). "Frequent epigenetic inactivation of cystatin M in breast carcinoma.". Oncogene 26 (21): 3089–94. doi:10.1038/sj.onc.1210107. PMID 17099723.
- Rivenbark AG, Livasy CA, Boyd CE, et al. (2007). "Methylation-dependent silencing of CST6 in primary human breast tumors and metastatic lesions.". Exp. Mol. Pathol. 83 (2): 188–97. doi:10.1016/j.yexmp.2007.03.008. PMC 2693953. PMID 17540367. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2693953.