PTTG1
Securin is a protein that in humans is encoded by the PTTG1 gene.[1][2][3]
The encoded protein is a homolog of yeast securin proteins, which prevent separins from promoting sister chromatid separation. It is an anaphase-promoting complex (APC) substrate that associates with a separin until activation of the APC. The gene product has transforming activity in vitro and tumorigenic activity in vivo, and the gene is highly expressed in various tumors. The gene product contains 2 PXXP motifs, which are required for its transforming and tumorigenic activities, as well as for its stimulation of basic fibroblast growth factor expression. It also contains a destruction box (D box) that is required for its degradation by the APC. The acidic C-terminal region of the encoded protein can act as a transactivation domain. The gene product is mainly a cytosolic protein, although it partially localizes in the nucleus.[3]
Interactions
PTTG1 has been shown to interact with RPS10,[4] PTTG1IP,[5] DNAJA1,[4] Ku70[6] and P53.[7]
References
- ^ Dominguez A, Ramos-Morales F, Romero F, Rios RM, Dreyfus F, Tortolero M, Pintor-Toro JA (Nov 1998). "hpttg, a human homologue of rat pttg, is overexpressed in hematopoietic neoplasms. Evidence for a transcriptional activation function of hPTTG". Oncogene 17 (17): 2187–93. doi:10.1038/sj.onc.1202140. PMID 9811450.
- ^ Zhang X, Horwitz GA, Prezant TR, Valentini A, Nakashima M, Bronstein MD, Melmed S (Mar 1999). "Structure, expression, and function of human pituitary tumor-transforming gene (PTTG)". Mol Endocrinol 13 (1): 156–66. doi:10.1210/me.13.1.156. PMID 9892021.
- ^ a b "Entrez Gene: PTTG1 pituitary tumor-transforming 1". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=9232.
- ^ a b Pei, L (Jan. 1999). "Pituitary tumor-transforming gene protein associates with ribosomal protein S10 and a novel human homologue of DnaJ in testicular cells". J. Biol. Chem. (UNITED STATES) 274 (5): 3151–8. doi:10.1074/jbc.274.5.3151. ISSN 0021-9258. PMID 9915854.
- ^ Chien, W; Pei L (Jun. 2000). "A novel binding factor facilitates nuclear translocation and transcriptional activation function of the pituitary tumor-transforming gene product". J. Biol. Chem. (UNITED STATES) 275 (25): 19422–7. doi:10.1074/jbc.M910105199. ISSN 0021-9258. PMID 10781616.
- ^ Romero, F; Multon M C, Ramos-Morales F, Domínguez A, Bernal J A, Pintor-Toro J A, Tortolero M (Mar. 2001). "Human securin, hPTTG, is associated with Ku heterodimer, the regulatory subunit of the DNA-dependent protein kinase". Nucleic Acids Res. (England) 29 (6): 1300–7. doi:10.1093/nar/29.6.1300. PMC 29753. PMID 11238996. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=29753.
- ^ Bernal, Juan A; Luna Rosa, Espina Agueda, Lázaro Icíar, Ramos-Morales Francisco, Romero Francisco, Arias Carmen, Silva Augusto, Tortolero María, Pintor-Toro José A (Oct. 2002). "Human securin interacts with p53 and modulates p53-mediated transcriptional activity and apoptosis". Nat. Genet. (United States) 32 (2): 306–11. doi:10.1038/ng997. ISSN 1061-4036. PMID 12355087.
Further reading
- Yu R, Melmed S (2004). "Pituitary tumor transforming gene: an update". Frontiers of hormone research. Frontiers of Hormone Research 32: 175–85. doi:10.1159/000079044. ISBN 3-8055-7740-0. PMID 15281346.
- Tfelt-Hansen J, Kanuparthi D, Chattopadhyay N (2006). "The Emerging Role of Pituitary Tumor Transforming Gene in Tumorigenesis". Clinical medicine & research 4 (2): 130–7. doi:10.3121/cmr.4.2.130. PMC 1483889. PMID 16809406. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1483889.
- Pei L (1999). "Pituitary tumor-transforming gene protein associates with ribosomal protein S10 and a novel human homologue of DnaJ in testicular cells". J. Biol. Chem. 274 (5): 3151–8. doi:10.1074/jbc.274.5.3151. PMID 9915854.
- Kakar SS (1999). "Assignment of the human tumor transforming gene TUTR1 to chromosome band 5q35.1 by fluorescence in situ hybridization". Cytogenet. Cell Genet. 83 (1–2): 93–5. doi:10.1159/000015139. PMID 9925941.
- Zhang X, Horwitz GA, Heaney AP et al. (1999). "Pituitary tumor transforming gene (PTTG) expression in pituitary adenomas". J. Clin. Endocrinol. Metab. 84 (2): 761–7. doi:10.1210/jc.84.2.761. PMID 10022450.
- Lee IA, Seong C, Choe IS (1999). "Cloning and expression of human cDNA encoding human homologue of pituitary tumor transforming gene". Biochem. Mol. Biol. Int. 47 (5): 891–7. PMID 10365261.
- Kakar SS, Jennes L (1999). "Molecular cloning and characterization of the tumor transforming gene (TUTR1): a novel gene in human tumorigenesis". Cytogenet. Cell Genet. 84 (3–4): 211–6. doi:10.1159/000015261. PMID 10393434.
- Zou H, McGarry TJ, Bernal T, Kirschner MW (1999). "Identification of a vertebrate sister-chromatid separation inhibitor involved in transformation and tumorigenesis". Science 285 (5426): 418–22. doi:10.1126/science.285.5426.418. PMID 10411507.
- Kakar SS (2000). "Molecular cloning, genomic organization, and identification of the promoter for the human pituitary tumor transforming gene (PTTG)". Gene 240 (2): 317–24. doi:10.1016/S0378-1119(99)00446-1. PMID 10580151.
- Ramos-Morales F, Domínguez A, Romero F et al. (2000). "Cell cycle regulated expression and phosphorylation of hpttg proto-oncogene product". Oncogene 19 (3): 403–9. doi:10.1038/sj.onc.1203320. PMID 10656688.
- Chien W, Pei L (2000). "A novel binding factor facilitates nuclear translocation and transcriptional activation function of the pituitary tumor-transforming gene product". J. Biol. Chem. 275 (25): 19422–7. doi:10.1074/jbc.M910105199. PMID 10781616.
- Ishikawa H, Heaney AP, Yu R et al. (2001). "Human pituitary tumor-transforming gene induces angiogenesis". J. Clin. Endocrinol. Metab. 86 (2): 867–74. doi:10.1210/jc.86.2.867. PMID 11158059.
- Zur A, Brandeis M (2001). "Securin degradation is mediated by fzy and fzr, and is required for complete chromatid separation but not for cytokinesis". EMBO J. 20 (4): 792–801. doi:10.1093/emboj/20.4.792. PMC 145417. PMID 11179223. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=145417.
- Romero F, Multon MC, Ramos-Morales F et al. (2001). "Human securin, hPTTG, is associated with Ku heterodimer, the regulatory subunit of the DNA-dependent protein kinase". Nucleic Acids Res. 29 (6): 1300–7. doi:10.1093/nar/29.6.1300. PMC 29753. PMID 11238996. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=29753.
- Jallepalli PV, Waizenegger IC, Bunz F et al. (2001). "Securin is required for chromosomal stability in human cells". Cell 105 (4): 445–57. doi:10.1016/S0092-8674(01)00340-3. PMID 11371342.
- Hilioti Z, Chung YS, Mochizuki Y et al. (2001). "The anaphase inhibitor Pds1 binds to the APC/C-associated protein Cdc20 in a destruction box-dependent manner". Curr. Biol. 11 (17): 1347–52. doi:10.1016/S0960-9822(01)00399-2. PMID 11553328.
- Waizenegger I, Giménez-Abián JF, Wernic D, Peters JM (2003). "Regulation of human separase by securin binding and autocleavage". Curr. Biol. 12 (16): 1368–78. doi:10.1016/S0960-9822(02)01073-4. PMID 12194817.
- McCabe CJ, Boelaert K, Tannahill LA et al. (2002). "Vascular endothelial growth factor, its receptor KDR/Flk-1, and pituitary tumor transforming gene in pituitary tumors". J. Clin. Endocrinol. Metab. 87 (9): 4238–44. doi:10.1210/jc.2002-020309. PMID 12213878.