Differential modulatation of cellular and viral promoters by p73 and p53

  • Authors:
    • Debabrita Deb
    • Arpad Lanyi
    • Mariano Scian
    • Jane Keiger
    • Doris R. Brown
    • Derek Le Roith
    • Swati Palit Deb
    • Sumitra Deb
  • View Affiliations

  • Published online on: February 1, 2001     https://doi.org/10.3892/ijo.18.2.401
  • Pages: 401-409
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Abstract

p73 has been shown to transcriptionally activate genes positively responsive to wild-type p53. In order to undertake a comparative study of functions of p53 and p73 we have cloned the cDNA of p73 from MCF-7 cells. Adenovirus onco-protein E1A inhibits the transactivation by p73; a deletion mutant of E1A incapable of interacting with p300 and CREB-binding protein (CBP) fails to disrupt the transactivation. Furthermore, CBP increases the transactivation mediated by p73 suggesting that CBP may function as a co-activator and E1A inhibits p73-mediated transactivation by sequestering p300 or CBP. We show that p73 can transcriptionally inhibit a number of cellular and viral promoters. However, wild-type p53, p73 α and p73 β differ in their ability to inhibit transcriptional activity of different promoters. While wild-type p53 inhibits the promoters of the human cytomegalovirus (CMV) immediate-early gene, the long terminal repeat of human immunodeficiency virus type 1 (HIV LTR), human cyclin A (cyc A) gene, and insulin-like growth factor receptor I (IGF-I-R), p73 α only inhibits the HIV LTR and cyc A promoters significantly; and p73 β inhibits the CMV, HIV LTR and cyc A promoters. A mutant of p73 α having amino acid substitutions at positions 268 and 300 on the presumptive DNA-binding domain fails to transactivate the p21 promoter but represses the CMV and the HIV LTR promoter quite efficiently showing that the mechanisms of transactivation and repression by p73 are different. Interestingly, p73 α transactivates the IGF-I-R promoter, which is inhibited by wild-type p53; p73 β has no significant effect on this promoter. This is a unique situation where p73 α differs from p73 β as well as p53.

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February 2001
Volume 18 Issue 2

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Deb D, Lanyi A, Scian M, Keiger J, Brown DR, Le Roith D, Deb SP and Deb S: Differential modulatation of cellular and viral promoters by p73 and p53. Int J Oncol 18: 401-409, 2001
APA
Deb, D., Lanyi, A., Scian, M., Keiger, J., Brown, D.R., Le Roith, D. ... Deb, S. (2001). Differential modulatation of cellular and viral promoters by p73 and p53. International Journal of Oncology, 18, 401-409. https://doi.org/10.3892/ijo.18.2.401
MLA
Deb, D., Lanyi, A., Scian, M., Keiger, J., Brown, D. R., Le Roith, D., Deb, S. P., Deb, S."Differential modulatation of cellular and viral promoters by p73 and p53". International Journal of Oncology 18.2 (2001): 401-409.
Chicago
Deb, D., Lanyi, A., Scian, M., Keiger, J., Brown, D. R., Le Roith, D., Deb, S. P., Deb, S."Differential modulatation of cellular and viral promoters by p73 and p53". International Journal of Oncology 18, no. 2 (2001): 401-409. https://doi.org/10.3892/ijo.18.2.401