[en] We have isolated and characterized two novel cDNAs encoding C2H2 zinc finger proteins showing high sequence homology to PLAG1, a protein ectopically activated by promoter swapping or promoter substitution in pleomorphic adenomas with chromosomal abnormalities at chromosome 8q12. PLAG1 and the two new PLAG1 family members (PLAGL1 and PLAGL2) constitute a novel subfamily of zinc finger proteins that recognize DNA and/or RNA. To examine the potential of the three human proteins to modulate transcription, we constructed several PLAG/GAL4 DNA binding domain fusion proteins and measured their ability to activate transcription of a reporter gene construct in different mammalian cell lines and in yeast. Although the carboxyl-terminal part of PLAGL1 shows strong overall transcriptional activity in mesenchymal (COS-1) and epithelial cells (293), both PLAG1 and PLAGL2 transactivate in mesenchymal cells only if depleted from a repressing region. This effect is less profound in epithelial cells. These data suggest that the activation in pleomorphic adenomas of PLAG1 most likely results in uncontrolled activation of downstream target genes.
Disciplines :
Genetics & genetic processes
Author, co-author :
Kas, K.
Voz, Marianne ; Université de Liège - ULiège > Département des sciences de la vie > GIGA-R : Biologie et génétique moléculaire
Hensen, K.
Meyen, E.
Van de Ven, W. J.
Language :
English
Title :
Transcriptional activation capacity of the novel PLAG family of zinc finger proteins.
Publication date :
1998
Journal title :
Journal of Biological Chemistry
ISSN :
0021-9258
eISSN :
1083-351X
Publisher :
American Society for Biochemistry and Molecular Biology, Baltimore, United States - Maryland
Kas, K., Voz, M., Röjer, E., Aström, A.-K., Meyen, E., Stenman, G., and Van de Ven, W. J. M. (1997) Nat. Genet. 15, 170-174
Kas, K., Röijer, E., Voz, M., Meyen, E., Stenman, G., and Van de Ven, W. J. M. (1997) Genomics 43, 349-358
Cadigan, K. M., and Nusse, R. (1997) Genes Dev. 11, 3286-3305
Voz, M. L., Astrom, A.-K., Kas, K., Mark, J., Stenman, G., and Van de Ven, W. J. M. (1998) Oncogene 16, 1409-1416
Pieler, T., and Bellefroid, E. (1994) Mol. Biol. Rep. 20, 1-8
Altschul, S. F., Gish, W., Miller, W., Myers, E. W., and Lipman, D. J. (1990) J. Mol. Biol. 215, 403-410
Sadowski, I., Bell, B., Broad, P., and Hollis, M. (1992) Gene 118, 137-141
Peers, B., Leonard, J., Sharma, S., Teitelman, G., and Montminy, M. R. (1994) Mol. Endocrinol. 8, 1798-1806
Gietz, R. D., and Schiestl, R. H. (1995) Methods Mol. Cell Biol. 5, 255-269
Boguski, M. S. (1995) Trends Biochem. Sci. 20, 295-296
Evans, R. M., and Hollenberg, S. M. (1989) Cell 52, 1-3
Sandros, J., Stenman, G., and Mark, J. (1990) Cancer Genet Cytogenet. 44, 153-167
Abdollahi, A., Godwin, A. K., Miller, P. D., Getts, L. A., Schultz, D. C., Taguchi, T., Testa, J. R., and Hamilton, T. C. (1997a) Cancer Res. 57, 2029-2034
Abdollahi, A., Roberts, D., Godwin, A. K., Schultz, D. C., Sonoda, G., Testa, J. R., and Hamilton, T. C. (1997) Oncogene 14, 1973-1979
Spengler, D., Villalba, M., Hoffmann, A., Pantaloni, C., Houssami, S., Bockaert, J., and Journot, L. (1997) EMBO J. 16, 2814-2825
Rabbitts, T. H. (1994) Nature 372, 143-149
Triezenberg, S. (1995) Curr. Opin. Genet Dev. 5, 190-196
Mao, S., Neale, G. A. M., and Goorha, R. M. (1997) J. Biol. Chem. 272, 5594-5599
Milner, J., Ponder, B., Hughes-Davies, L., Seltmann, M., and Kouzarides, T. (1997) Nature 386, 772-773