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  • Oncogenomics
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Cloning and characterization of a novel gene PDRG that is differentially regulated by p53 and ultraviolet radiation

Oncogene volume 22, pages 7247–7257 (2003)Cite this article

Abstract

We report the cloning and characterization of a novel p53 and DNA damage-regulated gene (PDRG). The human and mouse PDRG sequences are highly homologous and contain open reading frames of 133 amino acids each with molecular masses of 15.5 and 15.3 kDa, respectively. PDRG codes for a novel protein that does not show similarity to any known protein in the databases. Human PDRG is predominantly expressed in normal testis and exhibits reduced but detectable expression in other organs. GFP-tagged PDRG was predominantly detected as aggregates that appeared to reside in a distinct subcellular compartment. PDRG mRNA was upregulated by ultraviolet radiation (UV) but downregulated by tumor suppressor p53. UV is known to transcriptionally upregulate the expression of certain genes by activating the transcription factor Oct-1, while p53 has been reported to suppress transcription of certain genes by directly binding to a novel head-to-tail response element. Cloning and sequence analysis of PDRG promoter revealed the presence of Oct-1-binding element and a putative head-to-tail-type p53-binding site. Indeed, UV as well as exogenous Oct-1 independently increased PDRG promoter activity, suggesting that UV could mediate PDRG upregulation via Oct-1. Exogenous wild-type p53 was found to downregulate the PDRG promoter activity indicating that wild-type p53 transcriptionally suppresses the expression of PDRG and may mediate its effect via the putative head-to-tail response element. Furthermore, stable expression of exogenous PDRG was found to decrease the clonogenic survival after UV irradiation, which highlights the significance of PDRG in facilitating UV-induced killing.

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Acknowledgements

We thank Dr Bert Vogelstein for providing the p53-inducible DLD1 colon cancer cell line, HCT116(p53+/+) and HCT116(p53−/−) cells, p53 expression vector and PG13-luc and MG15-luc reporter vectors. We also thank Dr Randy Corn for providing Oct-1 expression vector. This work was supported in part by the National Institutes of Health Grants CA86945, CA89043 and DK062136. The cDNA and promoter sequences corresponding to PDRG have been submitted to GenBank (Accession # AY286301, AY286302 and AY286303).

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  1. Department of Pharmacology, State University of New York, Upstate Medical University, Syracuse, 12310, NY, USA

    Xiuquan Luo, Ying Huang & M Saeed Sheikh

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  1. Xiuquan Luo
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  2. Ying Huang
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Correspondence to M Saeed Sheikh.

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Luo, X., Huang, Y. & Sheikh, M. Cloning and characterization of a novel gene PDRG that is differentially regulated by p53 and ultraviolet radiation. Oncogene 22, 7247–7257 (2003). https://doi.org/10.1038/sj.onc.1207010

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