Disruption of functions of wild-type p53 by hetero-oligomerization.

  • Authors:
    • D Deb
    • A S Chakraborti
    • A Lányi
    • D A Troyer
    • S Deb
  • View Affiliations

  • Published online on: September 1, 1999     https://doi.org/10.3892/ijo.15.3.413
  • Pages: 413-435
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Abstract

We report that a p53 segment (p53 del 1-293) containing the oligomerization domain interferes with the functions of wild-type p53. Wild-type p53 inhibits transcription mediated by human cytomegalovirus (CMV) immediate-early promoter significantly; however, co-expression of p53 del 1-293 drastically reduces this repression. We show that wild-type p53 forms hetero-oligomers with p53 del 1-293 suggesting that the hetero-oligomers are defective in repressing the CMV promoter. A synthetic promoter with p53-binding sites is transactivated significantly by wild-type p53. However, co-expression of p53 del 1-293 drastically reduces this activation. At a high concentration, a deletion mutant of wild-type p53 (del 393-327) defective in oligomerization transactivates efficiently a promoter with synthetic p53-binding sites. This transactivation remains unaffected by co-expression of p53 del 1-293. p53 del 393-327 also fails to hetero-oligomerize with p53 del 1-293 indicating that hetero-oligomerization is necessary for disruption of wild-type p53-mediated transactivation. Immunostaining experiments show that hetero-oligomerization does not lead to changes in localization of nuclear p53 demonstrating that delocalization of p53 is not the reason for inactivation. We also show that co-expression of p53 del 1-293 significantly reduces the G1/S arrest by wild-type p53 suggesting that a proper oligomeric form is necessary for wild-type p53-mediated cell cycle arrest. Thus, our work shows that hetero-oligomerization disrupts wild-type p53's biological functions and suggests a mechanism by which p53 mutants may disrupt functions of wild-type p53.

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Sep 1999
Volume 15 Issue 3

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

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Spandidos Publications style
Deb D, Chakraborti A, Lányi A, Troyer D and Deb S: Disruption of functions of wild-type p53 by hetero-oligomerization.. Int J Oncol 15: 413-435, 1999
APA
Deb, D., Chakraborti, A., Lányi, A., Troyer, D., & Deb, S. (1999). Disruption of functions of wild-type p53 by hetero-oligomerization.. International Journal of Oncology, 15, 413-435. https://doi.org/10.3892/ijo.15.3.413
MLA
Deb, D., Chakraborti, A., Lányi, A., Troyer, D., Deb, S."Disruption of functions of wild-type p53 by hetero-oligomerization.". International Journal of Oncology 15.3 (1999): 413-435.
Chicago
Deb, D., Chakraborti, A., Lányi, A., Troyer, D., Deb, S."Disruption of functions of wild-type p53 by hetero-oligomerization.". International Journal of Oncology 15, no. 3 (1999): 413-435. https://doi.org/10.3892/ijo.15.3.413