PTTG1

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Pituitary tumor-transforming 1
Identifiers
Symbols PTTG1 ; EAP1; HPTTG; PTTG; TUTR1
External IDs OMIM604147 MGI1353578 HomoloGene3110 GeneCards: PTTG1 Gene
RNA expression pattern
PBB GE PTTG1 203554 x at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 9232 30939
Ensembl ENSG00000164611 ENSMUSG00000020415
UniProt O95997 Q9CQJ7
RefSeq (mRNA) NM_001282382 NM_001131054
RefSeq (protein) NP_001269311 NP_001124526
Location (UCSC) Chr 5:
159.85 – 159.86 Mb
Chr 11:
43.42 – 43.43 Mb
PubMed search [1] [2]

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[edit]

PTTG1 has been shown to interact with RPS10,[4] PTTG1IP,[5] DNAJA1,[4] Ku70[6] and P53.[7]

Regulation[edit]

During Mitosis CDK1 phosphorylate PTTG1 at Ser-165.[8]PTTG1 is down-regulated in melanoma cells in response to the cyclin-dependent kinase inhibitor PHA-848125.[9]

References[edit]

  1. ^ Dominguez A, Ramos-Morales F, Romero F, Rios RM, Dreyfus F, Tortolero M, Pintor-Toro JA (November 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. 
  2. ^ Zhang X, Horwitz GA, Prezant TR, Valentini A, Nakashima M, Bronstein MD, Melmed S (March 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. 
  3. ^ a b "Entrez Gene: PTTG1 pituitary tumor-transforming 1". 
  4. ^ a b Pei, L (January 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. 
  5. ^ Chien, W; Pei L (June 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. 
  6. ^ Romero, F; Multon M C; Ramos-Morales F; Domínguez A; Bernal J A; Pintor-Toro J A; Tortolero M (March 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. 
  7. ^ Bernal, Juan A; Luna Rosa, Espina Agueda, Lázaro Icíar, Ramos-Morales Francisco, Romero Francisco, Arias Carmen, Silva Augusto, Tortolero María, Pintor-Toro José A (October 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. 
  8. ^ Ramos-Morales F, Domínguez A, Romero F, Luna R, Multon MC, Pintor-Toro JA, Tortolero M. (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. 
  9. ^ Caporali S, Alvino E, Levati L, Esposito AI, Ciomei M, Brasca MG, Del Bufalo D, Desideri M, Bonmassar E, Pfeffer U, D'Atri S. (2012). "Down-regulation of the PTTG1 proto-oncogene contributes to the melanoma suppressive effects of the cyclin-dependent kinase inhibitor PHA-848125.". Biochem Pharmacol 84 (5): 598–611. doi:10.1016/j.bcp.2012.06.004. PMID 22704958. 

Further reading[edit]