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Stabilization of p53 and transactivation of its target genes in response to replication blockade

Oncogene volume 21, pages 7226–7229 (2002)Cite this article

Abstract

Although it is clear that p53 plays a pivotal role in G1/G2 checkpoints to conserve genomic integrity, its role in S phase checkpoint is less well understood. Recently, it has been reported that p53 is transcriptionally impaired even though it is stabilized during replication blockade. However, the mechanisms underlying this phenomenon are not known. In the present study, it has been shown that p53 accumulates and transactivates its target genes such as p21, gadd45 and bax in response to replication blockade in normal and cancer cells. Lack of transcriptional activation under similar conditions in cells lacking p53 shows that p53-target gene activation during replication blockade is indeed p53-dependent. Further, transactivation of p21 in response to replication blockade by hydroxyurea and aphidicolin is similar to that in response to ionizing radiation except that the latter is more immediate compared to the response to replication blockade. These findings suggest that impairment of transcriptionally active p53 in response to replication blockade is not a general phenomenon.

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Acknowledgements

We thank Mr Charles Thomas of Institutional Flow Cytometry Core Facility for the cell cycle analysis. We thank Drs Michael Brattain, Roswell Park Cancer Institute, Buffalo, NY, USA, Susan Conrad, Michigan State University, East Lansing, MI, USA, Martha Stampfer, Lawrence Berkeley National Laboratory, Berkeley, CA, USA, for kindly providing the RKO and HCT116 cells, MCF7 cells, and HMEC184AA3 cells, respectively. This work was supported by NIH grant RO1 CA79911 to GM Das.

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  1. Gokul M Das

    Present address: Department of Pharmacology & Therapeutics, Roswell Park Cancer Institute, Elm & Carlton Streets, Buffalo, 14263, New York, USA

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  1. Department of Surgery, Molecular Oncology Research Program, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, 78229, Texas, TX, USA

    Bijaya K Nayak & Gokul M Das

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  1. Bijaya K Nayak
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Correspondence to Gokul M Das.

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Nayak, B., Das, G. Stabilization of p53 and transactivation of its target genes in response to replication blockade. Oncogene 21, 7226–7229 (2002). https://doi.org/10.1038/sj.onc.1205889

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