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]
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]
ReferencesEdit
^ abcGRCh38: Ensembl release 89: ENSG00000164611 - Ensembl, May 2017
^ abcGRCm38: 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.
^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.
^ abPei 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. PMC29753. 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 readingEdit
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. ISBN3-8055-7740-0. 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. PMC1483889. 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. PMC145417. 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. PMC29753. 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. 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. 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.
October 15, 2023
pttg1, securin, protein, that, humans, encoded, gene, identifiersaliases, eap1, hpttg, pttg, tutr1, pituitary, tumor, transforming, regulator, sister, chromatid, separation, securin, ecrarexternal, idsomim, 604147, 1353578, homologene, 3110, genecards, gene, l. Securin is a protein that in humans is encoded by the PTTG1 gene 5 6 7 PTTG1IdentifiersAliasesPTTG1 EAP1 HPTTG PTTG TUTR1 pituitary tumor transforming 1 PTTG1 regulator of sister chromatid separation securin ECRARExternal IDsOMIM 604147 MGI 1353578 HomoloGene 3110 GeneCards PTTG1Gene location Human Chr Chromosome 5 human 1 Band5q33 3Start160 421 855 bp 1 End160 428 739 bp 1 Gene location Mouse Chr Chromosome 11 mouse 2 Band11 11 B1 1Start43 311 077 bp 2 End43 317 078 bp 2 RNA expression patternBgeeHumanMouse ortholog Top expressed insecondary oocyteganglionic eminencespermcancellous bonebone marrowhair folliclecavity of mouthrectumleft lobe of thyroid glandthymusTop expressed inciliary bodysecondary oocyteretinal pigment epitheliumirisbloodprimitive streakankleotic placoderight ventriclemotor neuronMore reference expression dataBioGPSMore reference expression dataGene ontologyMolecular functionpeptidase inhibitor activity cysteine type endopeptidase inhibitor activity DNA binding transcription factor activity SH3 domain binding protein binding DNA binding transcription factor activity RNA polymerase II specificCellular componentcytoplasm nucleus cytosolBiological processchromosome segregation chromosome organization homologous chromosome segregation cellular response to DNA damage stimulus cell division spermatogenesis cell cycle anaphase promoting complex dependent catabolic process DNA repair regulation of transcription DNA templated negative regulation of peptidase activity negative regulation of endopeptidase activity regulation of transcription by RNA polymerase II transcription by RNA polymerase II negative regulation of mitotic sister chromatid separation ubiquitin dependent protein catabolic processSources Amigo QuickGOOrthologsSpeciesHumanMouseEntrez923230939EnsemblENSG00000164611ENSMUSG00000020415UniProtO95997Q6IAL9Q9CQJ7RefSeq mRNA NM 004219NM 001282382NM 001282383NM 001131054NM 013917NM 001362799RefSeq protein NP 001269311NP 001269312NP 004210NP 001269311 1NP 001269312 1NP 004210 1NP 001124526NP 038945NP 001349728Location UCSC Chr 5 160 42 160 43 MbChr 11 43 31 43 32 MbPubMed search 3 4 WikidataView Edit HumanView Edit Mouse Contents 1 Function 2 Interactions 3 Regulation 4 References 5 Further readingFunction EditThe 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 EditPTTG1 has been shown to interact with DNAJA1 8 Ku70 9 P53 10 PTTG1IP 11 and RPS10 8 Regulation EditDuring 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 Edit 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 Dominguez 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 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 Dominguez 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 Lazaro 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 Dominguez 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 EditYu 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 amp 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 Dominguez 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 Dominguez 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 doi 10 1016 S0960 9822 01 00399 2 PMID 11553328 S2CID 11420259 Waizenegger I Gimenez Abian JF Wernic D Peters JM Aug 2002 Regulation of human separase by securin binding and autocleavage Current Biology 12 16 1368 78 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 Retrieved from https en wikipedia org w index php title PTTG1 amp oldid 1170979827, wikipedia, wiki, book, books, library,
