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The ubiquitin–proteasome system regulates p53-mediated transcription at p21waf1 promoter

Oncogene volume 26, pages 4199–4208 (2007)Cite this article

Abstract

The ubiquitin (Ub)–proteasome system (UPS) promotes the proteasomal degradation of target proteins by decorating them with Ub labels. Emerging evidence indicates a role of UPS in regulating gene transcription. In this study, we provided evidence for the involvement of UPS in the transcriptional activation function of tumor suppressor p53. We showed that both ubiquitylation and proteasomal functions are required for efficient transcription mediated by p53. Disruption of transcription by actinomycin D, 5,6-dichloro-1-β-D-ribofuranosyl-benzimadazole or α-amanitin leads to accumulation of cellular p53 protein. Proteasome inhibition by MG132 increases the occupancy of p53 protein at p53-responsive p21waf1 promoter. In addition, the Sug-1 component of 19S proteasome physically interacts with p53 in vitro and in vivo. Moreover, in response to ultraviolet-induced DNA damage, both the 19S proteasomal components, Sug1 and S1, are recruited to p21waf1 promoter region in a kinetic pattern similar to that of p53. These results suggested that UPS positively regulates p53-mediated transcription at p21waf1 promoter.

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Acknowledgements

We thank Drs Bert Vogelstein for p53 expression constructs and p53-responsive reporters, Moshe Oren for GAL4-p53 constructs, Jeffrey E Kudlow for GST-Sug-1 constructs. We also thank Drs Michael Tainsky for providing Li–Fraumeni syndrome cell lines and Fumio Hanaoka for providing FM3A and ts85 cell lines. We are grateful to Dr Jianming Chen for help with some pull-down experiments and Dr Song Qin for critical reading of the manuscript. The work was supported by Public Health Service Grants ES02388 and ES12991 from NIEHS and CA93413 from NCI.

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  1. J Yao

    Present address: 4Current Address: Department of Pharmacology, Dalian Medical University, Dalian, Liaoning 116027, China.,

Authors and Affiliations

  1. Department of Radiology, The Ohio State University, Columbus, OH, USA

    Q Zhu, G Wani, J Yao, S Patnaik, Q-E Wang, M A El-Mahdy, M Prætorius-Ibba & A A Wani

  2. Department of Molecular and Cellular Biochemistry, The Ohio State University, Columbus, OH, USA

    A A Wani

  3. The Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA

    A A Wani

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc).

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Zhu, Q., Wani, G., Yao, J. et al. The ubiquitin–proteasome system regulates p53-mediated transcription at p21waf1 promoter. Oncogene 26, 4199–4208 (2007). https://doi.org/10.1038/sj.onc.1210191

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