Securin is a protein that in humans is encoded by the PTTG1 gene. [5] [6] [7]
Function
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. [7]
Interactions
PTTG1 has been shown to interact with:
Regulation
During Mitosis CDK1 phosphorylate PTTG1 at Ser-165. [12] PTTG1 is down-regulated in melanoma cells in response to the cyclin-dependent kinase inhibitor PHA-848125. [13]
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000164611 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000020415 – 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.
- ^ Domínguez A, Ramos-Morales F, Romero F, Rios RM, Dreyfus F, Tortolero M, Pintor-Toro JA (Oct 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. S2CID 24151303.
- ^ Zhang X, Horwitz GA, Prezant TR, Valentini A, Nakashima M, Bronstein MD, Melmed S (Jan 1999). "Structure, expression, and function of human pituitary tumor-transforming gene (PTTG)". Molecular Endocrinology. 13 (1): 156–66. doi: 10.1210/me.13.1.156. PMID 9892021.
- ^ a b "Entrez Gene: PTTG1 pituitary tumor-transforming 1".
- ^ 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". The Journal of Biological Chemistry. 274 (5): 3151–8. doi: 10.1074/jbc.274.5.3151. PMID 9915854.
- ^ Romero F, Multon MC, Ramos-Morales F, Domínguez A, Bernal JA, Pintor-Toro JA, Tortolero M (Mar 2001). "Human securin, hPTTG, is associated with Ku heterodimer, the regulatory subunit of the DNA-dependent protein kinase". Nucleic Acids Research. 29 (6): 1300–7. doi: 10.1093/nar/29.6.1300. PMC 29753. PMID 11238996.
- ^ Bernal JA, Luna R, Espina A, Lázaro I, Ramos-Morales F, Romero F, Arias C, Silva A, Tortolero M, Pintor-Toro JA (Oct 2002). "Human securin interacts with p53 and modulates p53-mediated transcriptional activity and apoptosis". Nature Genetics. 32 (2): 306–11. doi: 10.1038/ng997. PMID 12355087. S2CID 1770399.
- ^ Chien W, Pei L (Jun 2000). "A novel binding factor facilitates nuclear translocation and transcriptional activation function of the pituitary tumor-transforming gene product". The Journal of Biological Chemistry. 275 (25): 19422–7. doi: 10.1074/jbc.M910105199. PMID 10781616.
- ^ Ramos-Morales F, Domínguez A, Romero F, Luna R, Multon MC, Pintor-Toro JA, Tortolero M (Jan 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. S2CID 21958836.
- ^ Caporali S, Alvino E, Levati L, Esposito AI, Ciomei M, Brasca MG, Del Bufalo D, Desideri M, Bonmassar E, Pfeffer U, D'Atri S (Sep 2012). "Down-regulation of the PTTG1 proto-oncogene contributes to the melanoma suppressive effects of the cyclin-dependent kinase inhibitor PHA-848125". Biochemical Pharmacology. 84 (5): 598–611. doi: 10.1016/j.bcp.2012.06.004. PMID 22704958.
Further reading
- Yu R, Melmed S (2004). "Pituitary tumor transforming gene: an update". Molecular Pathology of the Pituitary. Frontiers of Hormone Research. Vol. 32. pp. 175–85. doi: 10.1159/000079044. ISBN 3-8055-7740-0. PMID 15281346.
- Tfelt-Hansen J, Kanuparthi D, Chattopadhyay N (Jun 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.
- Pei L (Jan 1999). "Pituitary tumor-transforming gene protein associates with ribosomal protein S10 and a novel human homologue of DnaJ in testicular cells". The Journal of Biological Chemistry. 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". Cytogenetics and Cell Genetics. 83 (1–2): 93–5. doi: 10.1159/000015139. PMID 9925941. S2CID 28589466.
- Zhang X, Horwitz GA, Heaney AP, Nakashima M, Prezant TR, Bronstein MD, Melmed S (Feb 1999). "Pituitary tumor transforming gene (PTTG) expression in pituitary adenomas". The Journal of Clinical Endocrinology and Metabolism. 84 (2): 761–7. doi: 10.1210/jc.84.2.761. PMID 10022450.
- Lee IA, Seong C, Choe IS (May 1999). "Cloning and expression of human cDNA encoding human homologue of pituitary tumor transforming gene". Biochemistry and Molecular Biology International. 47 (5): 891–7. doi: 10.1080/15216549900201993. PMID 10365261. S2CID 22575138.
- Kakar SS, Jennes L (1999). "Molecular cloning and characterization of the tumor transforming gene (TUTR1): a novel gene in human tumorigenesis". Cytogenetics and Cell Genetics. 84 (3–4): 211–6. doi: 10.1159/000015261. PMID 10393434. S2CID 38980080.
- Zou H, McGarry TJ, Bernal T, Kirschner MW (Jul 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 (Nov 1999). "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, Luna R, Multon MC, Pintor-Toro JA, Tortolero M (Jan 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. S2CID 21958836.
- Chien W, Pei L (Jun 2000). "A novel binding factor facilitates nuclear translocation and transcriptional activation function of the pituitary tumor-transforming gene product". The Journal of Biological Chemistry. 275 (25): 19422–7. doi: 10.1074/jbc.M910105199. PMID 10781616.
- Ishikawa H, Heaney AP, Yu R, Horwitz GA, Melmed S (Feb 2001). "Human pituitary tumor-transforming gene induces angiogenesis". The Journal of Clinical Endocrinology and Metabolism. 86 (2): 867–74. doi: 10.1210/jcem.86.2.7184. PMID 11158059.
- Zur A, Brandeis M (Feb 2001). "Securin degradation is mediated by fzy and fzr, and is required for complete chromatid separation but not for cytokinesis". The EMBO Journal. 20 (4): 792–801. doi: 10.1093/emboj/20.4.792. PMC 145417. PMID 11179223.
- Romero F, Multon MC, Ramos-Morales F, Domínguez A, Bernal JA, Pintor-Toro JA, Tortolero M (Mar 2001). "Human securin, hPTTG, is associated with Ku heterodimer, the regulatory subunit of the DNA-dependent protein kinase". Nucleic Acids Research. 29 (6): 1300–7. doi: 10.1093/nar/29.6.1300. PMC 29753. PMID 11238996.
- Jallepalli PV, Waizenegger IC, Bunz F, Langer S, Speicher MR, Peters JM, Kinzler KW, Vogelstein B, Lengauer C (May 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. S2CID 16188959.
- Hilioti Z, Chung YS, Mochizuki Y, Hardy CF, Cohen-Fix O (Sep 2001). "The anaphase inhibitor Pds1 binds to the APC/C-associated protein Cdc20 in a destruction box-dependent manner". Current Biology. 11 (17): 1347–52. Bibcode: 2001CBio...11.1347H. doi: 10.1016/S0960-9822(01)00399-2. PMID 11553328. S2CID 11420259.
- Waizenegger I, Giménez-Abián JF, Wernic D, Peters JM (Aug 2002). "Regulation of human separase by securin binding and autocleavage". Current Biology. 12 (16): 1368–78. Bibcode: 2002CBio...12.1368W. doi: 10.1016/S0960-9822(02)01073-4. PMID 12194817. S2CID 18316557.
- McCabe CJ, Boelaert K, Tannahill LA, Heaney AP, Stratford AL, Khaira JS, Hussain S, Sheppard MC, Franklyn JA, Gittoes NJ (Sep 2002). "Vascular endothelial growth factor, its receptor KDR/Flk-1, and pituitary tumor transforming gene in pituitary tumors". The Journal of Clinical Endocrinology and Metabolism. 87 (9): 4238–44. doi: 10.1210/jc.2002-020309. PMID 12213878.
| PTTG1 | |||||||||||||||||||||||||||||||||||||||||||||||||||
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| Identifiers | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Aliases | PTTG1, EAP1, HPTTG, PTTG, TUTR1, pituitary tumor-transforming 1, PTTG1 regulator of sister chromatid separation, securin, ECRAR | ||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | OMIM: 604147 MGI: 1353578 HomoloGene: 3110 GeneCards: PTTG1 | ||||||||||||||||||||||||||||||||||||||||||||||||||
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| Wikidata | |||||||||||||||||||||||||||||||||||||||||||||||||||
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Securin is a protein that in humans is encoded by the PTTG1 gene. [5] [6] [7]
Function
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. [7]
Interactions
PTTG1 has been shown to interact with:
Regulation
During Mitosis CDK1 phosphorylate PTTG1 at Ser-165. [12] PTTG1 is down-regulated in melanoma cells in response to the cyclin-dependent kinase inhibitor PHA-848125. [13]
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000164611 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000020415 – 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.
- ^ Domínguez A, Ramos-Morales F, Romero F, Rios RM, Dreyfus F, Tortolero M, Pintor-Toro JA (Oct 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. S2CID 24151303.
- ^ Zhang X, Horwitz GA, Prezant TR, Valentini A, Nakashima M, Bronstein MD, Melmed S (Jan 1999). "Structure, expression, and function of human pituitary tumor-transforming gene (PTTG)". Molecular Endocrinology. 13 (1): 156–66. doi: 10.1210/me.13.1.156. PMID 9892021.
- ^ a b "Entrez Gene: PTTG1 pituitary tumor-transforming 1".
- ^ 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". The Journal of Biological Chemistry. 274 (5): 3151–8. doi: 10.1074/jbc.274.5.3151. PMID 9915854.
- ^ Romero F, Multon MC, Ramos-Morales F, Domínguez A, Bernal JA, Pintor-Toro JA, Tortolero M (Mar 2001). "Human securin, hPTTG, is associated with Ku heterodimer, the regulatory subunit of the DNA-dependent protein kinase". Nucleic Acids Research. 29 (6): 1300–7. doi: 10.1093/nar/29.6.1300. PMC 29753. PMID 11238996.
- ^ Bernal JA, Luna R, Espina A, Lázaro I, Ramos-Morales F, Romero F, Arias C, Silva A, Tortolero M, Pintor-Toro JA (Oct 2002). "Human securin interacts with p53 and modulates p53-mediated transcriptional activity and apoptosis". Nature Genetics. 32 (2): 306–11. doi: 10.1038/ng997. PMID 12355087. S2CID 1770399.
- ^ Chien W, Pei L (Jun 2000). "A novel binding factor facilitates nuclear translocation and transcriptional activation function of the pituitary tumor-transforming gene product". The Journal of Biological Chemistry. 275 (25): 19422–7. doi: 10.1074/jbc.M910105199. PMID 10781616.
- ^ Ramos-Morales F, Domínguez A, Romero F, Luna R, Multon MC, Pintor-Toro JA, Tortolero M (Jan 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. S2CID 21958836.
- ^ Caporali S, Alvino E, Levati L, Esposito AI, Ciomei M, Brasca MG, Del Bufalo D, Desideri M, Bonmassar E, Pfeffer U, D'Atri S (Sep 2012). "Down-regulation of the PTTG1 proto-oncogene contributes to the melanoma suppressive effects of the cyclin-dependent kinase inhibitor PHA-848125". Biochemical Pharmacology. 84 (5): 598–611. doi: 10.1016/j.bcp.2012.06.004. PMID 22704958.
Further reading
- Yu R, Melmed S (2004). "Pituitary tumor transforming gene: an update". Molecular Pathology of the Pituitary. Frontiers of Hormone Research. Vol. 32. pp. 175–85. doi: 10.1159/000079044. ISBN 3-8055-7740-0. PMID 15281346.
- Tfelt-Hansen J, Kanuparthi D, Chattopadhyay N (Jun 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.
- Pei L (Jan 1999). "Pituitary tumor-transforming gene protein associates with ribosomal protein S10 and a novel human homologue of DnaJ in testicular cells". The Journal of Biological Chemistry. 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". Cytogenetics and Cell Genetics. 83 (1–2): 93–5. doi: 10.1159/000015139. PMID 9925941. S2CID 28589466.
- Zhang X, Horwitz GA, Heaney AP, Nakashima M, Prezant TR, Bronstein MD, Melmed S (Feb 1999). "Pituitary tumor transforming gene (PTTG) expression in pituitary adenomas". The Journal of Clinical Endocrinology and Metabolism. 84 (2): 761–7. doi: 10.1210/jc.84.2.761. PMID 10022450.
- Lee IA, Seong C, Choe IS (May 1999). "Cloning and expression of human cDNA encoding human homologue of pituitary tumor transforming gene". Biochemistry and Molecular Biology International. 47 (5): 891–7. doi: 10.1080/15216549900201993. PMID 10365261. S2CID 22575138.
- Kakar SS, Jennes L (1999). "Molecular cloning and characterization of the tumor transforming gene (TUTR1): a novel gene in human tumorigenesis". Cytogenetics and Cell Genetics. 84 (3–4): 211–6. doi: 10.1159/000015261. PMID 10393434. S2CID 38980080.
- Zou H, McGarry TJ, Bernal T, Kirschner MW (Jul 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 (Nov 1999). "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, Luna R, Multon MC, Pintor-Toro JA, Tortolero M (Jan 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. S2CID 21958836.
- Chien W, Pei L (Jun 2000). "A novel binding factor facilitates nuclear translocation and transcriptional activation function of the pituitary tumor-transforming gene product". The Journal of Biological Chemistry. 275 (25): 19422–7. doi: 10.1074/jbc.M910105199. PMID 10781616.
- Ishikawa H, Heaney AP, Yu R, Horwitz GA, Melmed S (Feb 2001). "Human pituitary tumor-transforming gene induces angiogenesis". The Journal of Clinical Endocrinology and Metabolism. 86 (2): 867–74. doi: 10.1210/jcem.86.2.7184. PMID 11158059.
- Zur A, Brandeis M (Feb 2001). "Securin degradation is mediated by fzy and fzr, and is required for complete chromatid separation but not for cytokinesis". The EMBO Journal. 20 (4): 792–801. doi: 10.1093/emboj/20.4.792. PMC 145417. PMID 11179223.
- Romero F, Multon MC, Ramos-Morales F, Domínguez A, Bernal JA, Pintor-Toro JA, Tortolero M (Mar 2001). "Human securin, hPTTG, is associated with Ku heterodimer, the regulatory subunit of the DNA-dependent protein kinase". Nucleic Acids Research. 29 (6): 1300–7. doi: 10.1093/nar/29.6.1300. PMC 29753. PMID 11238996.
- Jallepalli PV, Waizenegger IC, Bunz F, Langer S, Speicher MR, Peters JM, Kinzler KW, Vogelstein B, Lengauer C (May 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. S2CID 16188959.
- Hilioti Z, Chung YS, Mochizuki Y, Hardy CF, Cohen-Fix O (Sep 2001). "The anaphase inhibitor Pds1 binds to the APC/C-associated protein Cdc20 in a destruction box-dependent manner". Current Biology. 11 (17): 1347–52. Bibcode: 2001CBio...11.1347H. doi: 10.1016/S0960-9822(01)00399-2. PMID 11553328. S2CID 11420259.
- Waizenegger I, Giménez-Abián JF, Wernic D, Peters JM (Aug 2002). "Regulation of human separase by securin binding and autocleavage". Current Biology. 12 (16): 1368–78. Bibcode: 2002CBio...12.1368W. doi: 10.1016/S0960-9822(02)01073-4. PMID 12194817. S2CID 18316557.
- McCabe CJ, Boelaert K, Tannahill LA, Heaney AP, Stratford AL, Khaira JS, Hussain S, Sheppard MC, Franklyn JA, Gittoes NJ (Sep 2002). "Vascular endothelial growth factor, its receptor KDR/Flk-1, and pituitary tumor transforming gene in pituitary tumors". The Journal of Clinical Endocrinology and Metabolism. 87 (9): 4238–44. doi: 10.1210/jc.2002-020309. PMID 12213878.