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Gene Review

PLAG1  -  pleiomorphic adenoma gene 1

Homo sapiens

Synonyms: PSA, Pleiomorphic adenoma gene 1 protein, SGPA, ZNF912, Zinc finger protein PLAG1
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Disease relevance of PLAG1


High impact information on PLAG1

  • Due to the t(3;8)(p21;q12), PLAG1 is activated and expression levels of CTNNB1 are reduced [1].
  • Our results indicate that PLAG1 activation due to promoter swapping is a crucial event in salivary gland tumourigenesis [1].
  • We here demonstrate that the t(3;8)(p21;q12) results in promoter swapping between PLAG1, a novel, developmentally regulated zinc finger gene at 8q12, and the constitutively expressed gene for beta-catenin (CTNNB1), a protein interface functioning in the WG/WNT signalling pathway and specification of cell fate during embryogenesis [1].
  • Pleiomorphic adenoma of the salivary glands is a benign epithelial tumour occurring primarily in the major and minor salivary glands [1].
  • CIS genes included members of a zinc finger transcription factors family, Plag1 and Plagl2, with eight and two independent insertions, respectively [6].

Biological context of PLAG1


Anatomical context of PLAG1

  • Crossbreeding of PTMS1 or PTMS2 mice with MMTV-Cre transgenic mice was done to target PLAG1 overexpression to salivary and mammary glands, in the P1-Mcre/P2-Mcre offspring [10].
  • Moreover, we found that PLAG1 can activate the transcription of mouse but not human beta-catenin in the 3T3 cells cotransfected with reporter constructs [11].
  • We also demonstrate that PLAG1 alterations are found in a spectrum of mesenchymal cell types in lipoblastomas, including lipoblasts, mature adipocytes, primitive mesenchymal cells, and fibroblast-like cells [12].
  • We also investigated the status of the PLAG1 gene in four cases (one PA, one CaPA, one adenoid cystic carcinoma, and one mucoepidermoid carcinoma) with 8q12 rearrangements [13].
  • PLAG1 encodes a zinc finger protein and was initially reported to be expressed in placenta and fetal tissues, with no detectable expression in other normal adult tissues [14].

Associations of PLAG1 with chemical compounds

  • Finally, mutation of three lysine residues in sumoylation motifs significantly impairs the transformation ability of PLAG1 and PLAGL2, suggesting the essential roles of these sites in the oncogenic potential of PLAG proteins [9].
  • To gain insight into molecular mechanisms regulating PLAG transcriptional capacity, we searched for interaction partners using the yeast two-hybrid system and confirmed these by glutathione S-transferase pull-down [8].
  • Pleiomorphic adenoma revealed reaction products in luminal tumour cells, the non-luminal or modified myoepithelial cells and their plasmacytoid variants, squamous metaplastic cells and chondroid cells [15].
  • The three-dimensional structures of the bacterial serine proteases SGPA, SGPB, and alpha-lytic protease have been compared with those of the pancreatic enzymes alpha-chymotrypsin and elastase [16].

Physical interactions of PLAG1

  • We show that PLAG1 binds IGF-II promoter 3 and stimulates its activity [17].
  • The XRCC1 IVS10+141G>A locus is centered in a sequence that is nearly identical to the consensus binding site for the PLAG1 transcription factor [18].

Regulatory relationships of PLAG1


Other interactions of PLAG1

  • Finally, PLAG1 and PLAGL2 expression was increased in 20% of human AML samples [21].
  • Together with PLAGL1 and PLAGL2, PLAG1 belongs to a subfamily of C(2)H(2) zinc finger transcription factors that activate transcription through binding to the bipartite consensus sequence GRGGC(N)(6-8)GGG [8].
  • In order to assess the importance of other translocation partner genes of PLAG1, and their possible relationship to CTNNB1, we have characterized a second recurrent translocation, i.e. the t(5;8)(p13;q12) [19].
  • This translocation leads to ectopic expression of a chimeric transcript consisting of sequences from the ubiquitously expressed gene for the leukemia inhibitory factor receptor (LIFR) and PLAG1 [19].
  • By mutating predicted SUMO consensus sites, we defined two important target lysines for SUMOylation in PLAG1, Lys-244 and Lys-263 [8].

Analytical, diagnostic and therapeutic context of PLAG1


  1. Promoter swapping between the genes for a novel zinc finger protein and beta-catenin in pleiomorphic adenomas with t(3;8)(p21;q12) translocations. Kas, K., Voz, M.L., Röijer, E., Aström, A.K., Meyen, E., Stenman, G., Van de Ven, W.J. Nat. Genet. (1997) [Pubmed]
  2. Transcriptional activation capacity of the novel PLAG family of zinc finger proteins. Kas, K., Voz, M.L., Hensen, K., Meyen, E., Van de Ven, W.J. J. Biol. Chem. (1998) [Pubmed]
  3. Amplification of MGC2177, PLAG1, PSMC6P, and LYN in a malignant mixed tumor of salivary gland detected by cDNA microarray with tyramide signal amplification. Tsang, Y.T., Chang, Y.M., Lu, X., Rao, P.H., Lau, C.C., Wong, K.K. Cancer Genet. Cytogenet. (2004) [Pubmed]
  4. Conserved mechanism of PLAG1 activation in salivary gland tumors with and without chromosome 8q12 abnormalities: identification of SII as a new fusion partner gene. Aström, A.K., Voz, M.L., Kas, K., Röijer, E., Wedell, B., Mandahl, N., Van de Ven, W., Mark, J., Stenman, G. Cancer Res. (1999) [Pubmed]
  5. Amplification and overexpression of the IGF2 regulator PLAG1 in hepatoblastoma. Zatkova, A., Rouillard, J.M., Hartmann, W., Lamb, B.J., Kuick, R., Eckart, M., von Schweinitz, D., Koch, A., Fonatsch, C., Pietsch, T., Hanash, S.M., Wimmer, K. Genes Chromosomes Cancer (2004) [Pubmed]
  6. Identification of genes that synergize with Cbfb-MYH11 in the pathogenesis of acute myeloid leukemia. Castilla, L.H., Perrat, P., Martinez, N.J., Landrette, S.F., Keys, R., Oikemus, S., Flanegan, J., Heilman, S., Garrett, L., Dutra, A., Anderson, S., Pihan, G.A., Wolff, L., Liu, P.P. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  7. The tumorigenic diversity of the three PLAG family members is associated with different DNA binding capacities. Hensen, K., Van Valckenborgh, I.C., Kas, K., Van de Ven, W.J., Voz, M.L. Cancer Res. (2002) [Pubmed]
  8. Repression of the Transactivating Capacity of the Oncoprotein PLAG1 by SUMOylation. Van Dyck, F., Delvaux, E.L., Van de Ven, W.J., Chavez, M.V. J. Biol. Chem. (2004) [Pubmed]
  9. Sumoylation and acetylation play opposite roles in the transactivation of PLAG1 and PLAGL2. Zheng, G., Yang, Y.C. J. Biol. Chem. (2005) [Pubmed]
  10. Salivary gland tumors in transgenic mice with targeted PLAG1 proto-oncogene overexpression. Declercq, J., Van Dyck, F., Braem, C.V., Van Valckenborgh, I.C., Voz, M., Wassef, M., Schoonjans, L., Van Damme, B., Fiette, L., Van de Ven, W.J. Cancer Res. (2005) [Pubmed]
  11. Wnt pathway is involved in pleomorphic adenomas induced by overexpression of PLAG1 in transgenic mice. Zhao, X., Ren, W., Yang, W., Wang, Y., Kong, H., Wang, L., Yan, L., Xu, G., Fei, J., Fu, J., Zhang, C., Wang, Z. Int. J. Cancer (2006) [Pubmed]
  12. PLAG1 alterations in lipoblastoma: involvement in varied mesenchymal cell types and evidence for alternative oncogenic mechanisms. Gisselsson, D., Hibbard, M.K., Dal Cin, P., Sciot, R., Hsi, B.L., Kozakewich, H.P., Fletcher, J.A. Am. J. Pathol. (2001) [Pubmed]
  13. Characterization of chromosome aberrations in salivary gland tumors by FISH, including multicolor COBRA-FISH. Jin, C., Martins, C., Jin, Y., Wiegant, J., Wennerberg, J., Dictor, M., Gisselsson, D., Strömbeck, B., Fonseca, I., Mitelman, F., Tanke, H.J., Höglund, M., Mertens, F. Genes Chromosomes Cancer (2001) [Pubmed]
  14. Pleomorphic adenoma gene 1 is expressed in cultured benign and malignant salivary gland tumor cells. Queimado, L., Lopes, C., Du, F., Martins, C., Bowcock, A.M., Soares, J., Lovett, M. Lab. Invest. (1999) [Pubmed]
  15. Immunohistochemical evaluation of transglutaminase C in tumours of salivary glands. Lee, C.H., Lee, S.K., Chi, J.G., Park, S.C., Chung, S.I., Saitoh, M., Shrestha, P., Mori, M. Eur. J. Cancer, B, Oral Oncol. (1996) [Pubmed]
  16. Amino acid sequence alignment of bacterial and mammalian pancreatic serine proteases based on topological equivalences. James, M.N., Delbaere, L.T., Brayer, G.D. Can. J. Biochem. (1978) [Pubmed]
  17. PLAG1, the main translocation target in pleomorphic adenoma of the salivary glands, is a positive regulator of IGF-II. Voz, M.L., Agten, N.S., Van de Ven, W.J., Kas, K. Cancer Res. (2000) [Pubmed]
  18. An intronic polymorphism associated with increased XRCC1 expression, reduced apoptosis and familial breast cancer. Bu, D., Tomlinson, G., Lewis, C.M., Zhang, C., Kildebeck, E., Euhus, D.M. Breast Cancer Res. Treat. (2006) [Pubmed]
  19. The recurrent translocation t(5;8)(p13;q12) in pleomorphic adenomas results in upregulation of PLAG1 gene expression under control of the LIFR promoter. Voz, M.L., Aström, A.K., Kas, K., Mark, J., Stenman, G., Van de Ven, W.J. Oncogene (1998) [Pubmed]
  20. Histologic localization of PLAG1 (pleomorphic adenoma gene 1) in pleomorphic adenoma of the salivary gland: cytogenetic evidence of common origin of phenotypically diverse cells. Debiec-Rychter, M., Van Valckenborgh, I., Van den Broeck, C., Hagemeijer, A., Van de Ven, W.J., Kas, K., Van Damme, B., Voz, M.L. Lab. Invest. (2001) [Pubmed]
  21. Plag1 and Plagl2 are oncogenes that induce acute myeloid leukemia in cooperation with Cbfb-MYH11. Landrette, S.F., Kuo, Y.H., Hensen, K., Barjesteh van Waalwijk van Doorn-Khosrovani, S., Perrat, P.N., Van de Ven, W.J., Delwel, R., Castilla, L.H. Blood (2005) [Pubmed]
  22. Fluorescence in situ hybridization mapping of breakpoints in pleomorphic adenomas with 8q12-13 abnormalities identifies a subgroup of tumors without PLAG1 involvement. Röijer, E., Kas, K., Behrendt, M., Van de Ven, W., Stenman, G. Genes Chromosomes Cancer (1999) [Pubmed]
  23. CHCHD7-PLAG1 and TCEA1-PLAG1 gene fusions resulting from cryptic, intrachromosomal 8q rearrangements in pleomorphic salivary gland adenomas. Asp, J., Persson, F., Kost-Alimova, M., Stenman, G. Genes Chromosomes Cancer (2006) [Pubmed]
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