This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wang, S. Articles by El-Deiry, W. S. Search for Related Content PubMed PubMed Citation Articles by Wang, S. Articles by El-Deiry, W. S.

p73 or p53 Directly Regulates Human p53 Transcription to Maintain Cell Cycle Checkpoints

Laboratory of Molecular Oncology and Cell Cycle Regulation, Departments of Medicine (Hematology/Oncology), Genetics, and Pharmacology, the Institute for Translational Medicine and Therapeutics, and the Abramson Comprehensive Cancer Center, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania

Requests for reprints: Wafik S. El-Deiry, University of Pennsylvania, 415 Curie Boulevard, CRB437A, Philadelphia, PA 19104. Phone: 215-898-9015; Fax: 215-573-9139; E-mail: wafik{at}mail.med.upenn.edu.

Whereas the p53 tumor suppressor protein plays a central role in cellular checkpoints that respond to damage or stress to prevent tumorigenesis, the transcriptional control of the p53 gene has remained unclear. We show that chemotherapeutic agents induce p53 transcription and that p73 or p53 transactivates endogenous p53 expression through direct binding to the p53 promoter. Silencing of p53 or p73 by RNA interference significantly suppresses p53 transcription under physiologic conditions or in response to cellular stress. Mutational analysis of the human p53 promoter localized a p53 DNA-binding site, which confers p53- or p73-dependent p53 promoter activation. Importantly, impaired p53-mediated autoregulation of p53 transcription by inducible-interfering RNA results in aberrant cell cycle regulation and suppression of p53-mediated apoptosis. Thus, a positive feedback loop regulates human p53 expression and involves p73 and p53. Disruption of p53 transcription contributes to defective checkpoint control. (Cancer Res 2006; 66(14): 6982-9)

This article has been cited by other articles:

				L. Chen, N. Iraci, S. Gherardi, L. D. Gamble, K. M. Wood, G. Perini, J. Lunec, and D. A. Tweddle p53 Is a Direct Transcriptional Target of MYCN in Neuroblastoma Cancer Res., February 15, 2010; 70(4): 1377 - 1388. [Abstract] [Full Text] [PDF]

				C.-S. Kim, S.-B. Jung, A. Naqvi, T. A. Hoffman, J. DeRicco, T. Yamamori, M. P. Cole, B.-H. Jeon, and K. Irani P53 Impairs Endothelium-Dependent Vasomotor Function Through Transcriptional Upregulation of P66shc Circ. Res., December 5, 2008; 103(12): 1441 - 1450. [Abstract] [Full Text] [PDF]

				M. Yan, Y. Song, C. P. Wong, K. Hardin, and E. Ho Zinc Deficiency Alters DNA Damage Response Genes in Normal Human Prostate Epithelial Cells J. Nutr., April 1, 2008; 138(4): 667 - 673. [Abstract] [Full Text] [PDF]

				R. Okoshi, T. Ozaki, H. Yamamoto, K. Ando, N. Koida, S. Ono, T. Koda, T. Kamijo, A. Nakagawara, and H. Kizaki Activation of AMP-activated Protein Kinase Induces p53-dependent Apoptotic Cell Death in Response to Energetic Stress J. Biol. Chem., February 15, 2008; 283(7): 3979 - 3987. [Abstract] [Full Text] [PDF]

				N. Eckstein, K. Servan, L. Girard, D. Cai, G. von Jonquieres, U. Jaehde, M. U. Kassack, A. F. Gazdar, J. D. Minna, and H.-D. Royer Epidermal Growth Factor Receptor Pathway Analysis Identifies Amphiregulin as a Key Factor for Cisplatin Resistance of Human Breast Cancer Cells J. Biol. Chem., January 11, 2008; 283(2): 739 - 750. [Abstract] [Full Text] [PDF]

				H. Liu, Z.-G. Lu, Y. Miki, and K. Yoshida Protein Kinase C {delta} Induces Transcription of the TP53 Tumor Suppressor Gene by Controlling Death-Promoting Factor Btf in the Apoptotic Response to DNA Damage Mol. Cell. Biol., December 15, 2007; 27(24): 8480 - 8491. [Abstract] [Full Text] [PDF]

				J. Zhang and X. Chen {Delta}Np73 Modulates Nerve Growth Factor-Mediated Neuronal Differentiation through Repression of TrkA Mol. Cell. Biol., May 15, 2007; 27(10): 3868 - 3880. [Abstract] [Full Text] [PDF]