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p73 transcriptional activity increases upon cooperation between its spliced forms

Oncogene volume 19, pages 831–835 (2000)Cite this article

Abstract

The p53 homologue p73 efficiently activates p53-responsive genes. The well documented over-expression of p73 spliced forms in a wide variety of tumor types promoted us to elucidate the mechanisms underlying p73-mediated transcription. Using the luciferase reporter gene driven by Mdm2-minimal promoter in p53 null cells, we demonstrate that the weak transcriptional activity mediated by p73α was increased by the mutant form p73β292, which by itself is transcriptionally inactive. Similarly, cooperation between p73β and an inactive form of p73α increased p73β-mediated transcriptional activities. Conversely, p73β elicited a silencing effect on a gain of function mutant, p53281, which by itself mediated efficient transactivation of the MDR promoter. Neither anisomycin nor actinomycin D altered p73-mediated transcriptional activities, whereas sorbitol profoundly inhibited them through a rapid proteasome-dependent degradation of p73. Our observations point to plausible scenarios in which p73, through cooperation between p73 spliced forms and suppression of gain of function mutant p53 may elicit changes in the transcription of p53 target genes that play key roles in cell growth and death.

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Acknowledgements

We thank W Kaelin Jr. for the p73 constructs. Support from NCI grant CA78419 (to Z Ronai) is gratefully acknowledged.

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Authors and Affiliations

  1. Ruttenberg Cancer Center, Mount Sinai School of Medicine, 1425 Madison Avenue, New York, 10029, NY, USA

    Dania Alarcon-Vargas, Serge Y Fuchs & Ze'ev Ronai

  2. Comprehensive Cancer Center, Wake Forrest University, Winston-Salem, NC 27157, North Carolina, USA

    Sumitra Deb

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  1. Dania Alarcon-Vargas
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  2. Serge Y Fuchs
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  3. Sumitra Deb
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  4. Ze'ev Ronai
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Alarcon-Vargas, D., Fuchs, S., Deb, S. et al. p73 transcriptional activity increases upon cooperation between its spliced forms. Oncogene 19, 831–835 (2000). https://doi.org/10.1038/sj.onc.1203311

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