PTTG1

Pituitary tumor-transforming 1
Identifiers
Symbols PTTG1 ; EAP1; HPTTG; PTTG; TUTR1
External IDs OMIM: 604147 MGI: 1353578 HomoloGene: 3110 GeneCards: PTTG1 Gene
RNA expression pattern
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:
160.42 – 160.43 Mb
Chr 11:
43.42 – 43.43 Mb
PubMed search

Securin is a protein that in humans is encoded by the PTTG1 gene.[1][2][3]

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.[3]

Interactions

PTTG1 has been shown to interact with:

Regulation

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

  1. 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.
  2. 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.
  3. 1 2 "Entrez Gene: PTTG1 pituitary tumor-transforming 1".
  4. 1 2 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. PMID 9915854.
  5. 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. PMC 29753. PMID 11238996.
  6. 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.
  7. 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.
  8. 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.
  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 (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

This article is issued from Wikipedia - version of the Sunday, November 29, 2015. The text is available under the Creative Commons Attribution/Share Alike but additional terms may apply for the media files.