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Gene Review

TPD52  -  tumor protein D52

Homo sapiens

Synonyms: D52, N8L, PC-1, PrLZ, Protein N8, ...
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Disease relevance of TPD52


Psychiatry related information on TPD52

  • The level of risk-taking behaviour in the aquarium study positively correlated with lake-specific PC1 scores [7].
  • Finally, an awareness of possible genetic causes of eating disorders will help determine the causes--and thus the treatments--in children and adolescents with eating disorders, as exemplified by obese patients with mutations in the POMC, PC1, leptin, and MC4R loci [8].

High impact information on TPD52

  • This 3 bp deletion (AAC) in exon 1 of K6a removes a highly conserved asparagine residue (delta N170) from position 8 of the 1A helical domain (delta N8) [9].
  • Antibody to PC-1, another ectoNTPPHase, reacted with 1% SDS extracts of whole chondrocytes but not against those chromatographic fractions containing the major portion of NTPPHase activity [10].
  • The present study demonstrates that stable expression of sst2 in the hamster pancreatic cancer cells PC-1 and PC-1.0 activates an autocrine negative loop leading to an in vitro inhibition of cell proliferation [11].
  • Human chondrocyte NTPPPH activity was largely attributable to plasma cell membrane glycoprotein 1, PC-1 [12].
  • In the Thiel myeloma cell line, TPD52 bound to annexin VI in a Ca(2+)-dependent manner, suggesting that these molecules may act in concert to regulate secretory processes in plasma cells, similarly to what was observed in pancreatic acinar cells [13].

Chemical compound and disease context of TPD52


Biological context of TPD52

  • The human D52 locus has been previously mapped to chromosome 8q21, and using in situ mapping in the present study, a human D53 locus was mapped to chromosome 6q22-q23 [19].
  • TPD52 therefore represents a novel molecular marker in ovarian cancer, which is broadly expressed across the different histologic subtypes and whose upregulation frequently reflects increased TPD52 copy number [2].
  • In an independent cohort of stage III serous carcinomas (n = 18), we also directly compared in situ TPD52 expression using immunohistochemistry and TPD52 copy number using interphase FISH analyses [2].
  • Thus, D52-like proteins appear to exert and/or regulate their activities through specific interactions with other D52-like proteins, which in turn may be intrinsic to potential roles of these molecules in controlling cell proliferation [20].
  • D52-like gene transcripts are subject to alternative splicing, with sequences encoding a region termed insert 3 being affected in all three D52-like genes [21].

Anatomical context of TPD52

  • Our study has therefore identified a novel member of the MAL proteolipid family and potentially implicates TPD52-like proteins in vesicle transport [22].
  • Tumor protein D52 (TPD52): a novel B-cell/plasma-cell molecule with unique expression pattern and Ca(2+)-dependent association with annexin VI [13].
  • TPD52 expression pattern in normal and neoplastic B cells was unique [13].
  • These analyses revealed that all normal ovarian epithelium samples and benign serous tumors were predominantly TPD52-negative, whereas TPD52 was overexpressed in most (44/57; 77%) ovarian carcinomas regardless of histologic subtype [2].
  • Monoclonal anti-PrLZ antibodies were produced and intense immunohistochemical staining of PrLZ was observed in prostate epithelial cells in intraepithelial neoplasia and prostate cancer, whereas lower-level staining was detected in normal and benign epithelial components of the prostate gland [1].

Associations of TPD52 with chemical compounds

  • Two-dimensional polyacrylamide gel electrophoresis (2D-PAGE)/mass-spectrometry analysis identified the 28-kDa protein as human tumor protein D52 (TPD52), whose expression had been previously described only in normal and neoplastic epithelia [13].
  • Since D52-like protein sequences are all predicted to contain a coiled-coil domain, we used the yeast two-hybrid system and glutathione S-transferase pull-down assays to investigate whether homo- and/or heteromeric interactions occur between D52-like proteins [20].
  • Furthermore, our studies suggest that TPD52 protein levels may be regulated by androgens, consistent with the presence of androgen response elements in the upstream promoter of TPD52 [23].
  • These results suggest that cell motility of low-invasive PC-1 cells is under control through cyclic AMP-dependent protein kinase A, while the protein kinase C pathway seems favorable for high-invasive PC-1.0 cells to maintain the continuously enhanced cell motility responsible for their high invasiveness [24].
  • Interleukin 1 beta suppresses transforming growth factor-induced inorganic pyrophosphate (PPi) production and expression of the PPi-generating enzyme PC-1 in human chondrocytes [12].

Other interactions of TPD52


Analytical, diagnostic and therapeutic context of TPD52


  1. PrLZ, a novel prostate-specific and androgen-responsive gene of the TPD52 family, amplified in chromosome 8q21.1 and overexpressed in human prostate cancer. Wang, R., Xu, J., Saramäki, O., Visakorpi, T., Sutherland, W.M., Zhou, J., Sen, B., Lim, S.D., Mabjeesh, N., Amin, M., Dong, J.T., Petros, J.A., Nelson, P.S., Marshall, F.F., Zhau, H.E., Chung, L.W. Cancer Res. (2004) [Pubmed]
  2. Tumor protein D52 (TPD52) is overexpressed and a gene amplification target in ovarian cancer. Byrne, J.A., Balleine, R.L., Fejzo, M.S., Mercieca, J., Chiew, Y.E., Livnat, Y., St Heaps, L., Peters, G.B., Byth, K., Karlan, B.Y., Slamon, D.J., Harnett, P., Defazio, A. Int. J. Cancer (2005) [Pubmed]
  3. D53 (TPD52L1) is a cell cycle-regulated protein maximally expressed at the G2-M transition in breast cancer cells. Boutros, R., Byrne, J.A. Exp. Cell Res. (2005) [Pubmed]
  4. DNA copy number changes at 8q11-24 in metastasized colorectal cancer. Buffart, T.E., Coffa, J., Hermsen, M.A., Carvalho, B., van der Sijp, J.R., Ylstra, B., Pals, G., Schouten, J.P., Meijer, G.A. Cellular oncology : the official journal of the International Society for Cellular Oncology. (2005) [Pubmed]
  5. PrLZ is expressed in normal prostate development and in human prostate cancer progression. Wang, R., Xu, J., Mabjeesh, N., Zhu, G., Zhou, J., Amin, M., He, D., Marshall, F.F., Zhau, H.E., Chung, L.W. Clin. Cancer Res. (2007) [Pubmed]
  6. Nonredundant functions for tumor protein D52-like proteins support specific targeting of TPD52. Shehata, M., Bièche, I., Boutros, R., Weidenhofer, J., Fanayan, S., Spalding, L., Zeps, N., Byth, K., Bright, R.K., Lidereau, R., Byrne, J.A. Clin. Cancer Res. (2008) [Pubmed]
  7. Risk-taking behaviour in foraging young-of-the-year perch varies with population size structure. Magnhagen, C. Oecologia (2006) [Pubmed]
  8. The human genetics of eating disorders lessons from the leptin/melanocortin system. Costa, J.L., Brennen, M.B., Hochgeschwender, U. Child and adolescent psychiatric clinics of North America. (2002) [Pubmed]
  9. Mutation of a type II keratin gene (K6a) in pachyonychia congenita. Bowden, P.E., Haley, J.L., Kansky, A., Rothnagel, J.A., Jones, D.O., Turner, R.J. Nat. Genet. (1995) [Pubmed]
  10. A unique ectonucleotide pyrophosphohydrolase associated with porcine chondrocyte-derived vesicles. Masuda, I., Hamada, J., Haas, A.L., Ryan, L.M., McCarty, D.J. J. Clin. Invest. (1995) [Pubmed]
  11. Inhibition of growth and metastatic progression of pancreatic carcinoma in hamster after somatostatin receptor subtype 2 (sst2) gene expression and administration of cytotoxic somatostatin analog AN-238. Benali, N., Cordelier, P., Calise, D., Pages, P., Rochaix, P., Nagy, A., Esteve, J.P., Pour, P.M., Schally, A.V., Vaysse, N., Susini, C., Buscail, L. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  12. Interleukin 1 beta suppresses transforming growth factor-induced inorganic pyrophosphate (PPi) production and expression of the PPi-generating enzyme PC-1 in human chondrocytes. Lotz, M., Rosen, F., McCabe, G., Quach, J., Blanco, F., Dudler, J., Solan, J., Goding, J., Seegmiller, J.E., Terkeltaub, R. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  13. Tumor protein D52 (TPD52): a novel B-cell/plasma-cell molecule with unique expression pattern and Ca(2+)-dependent association with annexin VI. Tiacci, E., Orvietani, P.L., Bigerna, B., Pucciarini, A., Corthals, G.L., Pettirossi, V., Martelli, M.P., Liso, A., Benedetti, R., Pacini, R., Bolli, N., Pileri, S., Pulford, K., Gambacorta, M., Carbone, A., Pasquarello, C., Scherl, A., Robertson, H., Sciurpi, M.T., Alunni-Bistocchi, G., Binaglia, L., Byrne, J.A., Falini, B. Blood (2005) [Pubmed]
  14. Skeletal muscle content of membrane glycoprotein PC-1 in obesity. Relationship to muscle glucose transport. Youngren, J.F., Maddux, B.A., Sasson, S., Sbraccia, P., Tapscott, E.B., Swanson, M.S., Dohm, G.L., Goldfine, I.D. Diabetes (1996) [Pubmed]
  15. Production of scatter factor-like activity by a nitrosamine-induced pancreatic cancer cell line. Hirota, M., Egami, H., Corra, S., Fujii, H., Chaney, W.G., Rizzino, A., Pour, P.M. Carcinogenesis (1993) [Pubmed]
  16. Crystal structure of an acylation transition-state analog of the TEM-1 beta-lactamase. Mechanistic implications for class A beta-lactamases. Maveyraud, L., Pratt, R.F., Samama, J.P. Biochemistry (1998) [Pubmed]
  17. Inhibition of pancreatic cancer growth by the dietary isoprenoids farnesol and geraniol. Burke, Y.D., Stark, M.J., Roach, S.L., Sen, S.E., Crowell, P.L. Lipids (1997) [Pubmed]
  18. Characterization of cancer cell dissociation factor in a highly invasive pancreatic cancer cell line. Kurizaki, T., Egami, H., Hirota, M., Akagi, J., Ohmachi, H., Yamamoto, S., Ogawa, M. Cancer (1995) [Pubmed]
  19. Definition of the tumor protein D52 (TPD52) gene family through cloning of D52 homologues in human (hD53) and mouse (mD52). Byrne, J.A., Mattei, M.G., Basset, P. Genomics (1996) [Pubmed]
  20. Identification of homo- and heteromeric interactions between members of the breast carcinoma-associated D52 protein family using the yeast two-hybrid system. Byrne, J.A., Nourse, C.R., Basset, P., Gunning, P. Oncogene (1998) [Pubmed]
  21. Alternative splicing as a mechanism for regulating 14-3-3 binding: interactions between hD53 (TPD52L1) and 14-3-3 proteins. Boutros, R., Bailey, A.M., Wilson, S.H., Byrne, J.A. J. Mol. Biol. (2003) [Pubmed]
  22. Identification of MAL2, a novel member of the mal proteolipid family, though interactions with TPD52-like proteins in the yeast two-hybrid system. Wilson, S.H., Bailey, A.M., Nourse, C.R., Mattei, M.G., Byrne, J.A. Genomics (2001) [Pubmed]
  23. Overexpression, amplification, and androgen regulation of TPD52 in prostate cancer. Rubin, M.A., Varambally, S., Beroukhim, R., Tomlins, S.A., Rhodes, D.R., Paris, P.L., Hofer, M.D., Storz-Schweizer, M., Kuefer, R., Fletcher, J.A., Hsi, B.L., Byrne, J.A., Pienta, K.J., Collins, C., Sellers, W.R., Chinnaiyan, A.M. Cancer Res. (2004) [Pubmed]
  24. Signal transduction pathway of the induction of cell motility in hamster pancreatic ductal adenocarcinoma cell. Akagi, J., Egami, H., Kurizaki, T., Ohmachi, H., Ogawa, M. Invasion Metastasis (1997) [Pubmed]
  25. Cloning of a third member of the D52 gene family indicates alternative coding sequence usage in D52-like transcripts. Nourse, C.R., Mattei, M.G., Gunning, P., Byrne, J.A. Biochim. Biophys. Acta (1998) [Pubmed]
  26. Isolation and characterization of a novel gene expressed in multiple cancers. Chen, S.L., Maroulakou, I.G., Green, J.E., Romano-Spica, V., Modi, W., Lautenberger, J., Bhat, N.K. Oncogene (1996) [Pubmed]
  27. Characterization of human N8 protein. Chen, S.L., Zhang, X.K., Halverson, D.O., Byeon, M.K., Schweinfest, C.W., Ferris, D.K., Bhat, N.K. Oncogene (1997) [Pubmed]
  28. The hD52 (TPD52) gene is a candidate target gene for events resulting in increased 8q21 copy number in human breast carcinoma. Balleine, R.L., Fejzo, M.S., Sathasivam, P., Basset, P., Clarke, C.L., Byrne, J.A. Genes Chromosomes Cancer (2000) [Pubmed]
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