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 Kato, S. Articles by Ishioka, C. Search for Related Content PubMed PubMed Citation Articles by Kato, S. Articles by Ishioka, C.

Effects of p51/p63 Missense Mutations on Transcriptional Activities of p53 Downstream Gene Promoters¹

Departments of Clinical Oncology [S K., A S., R K., C I.] and Cell Biology [M Os., S I., M Ob.], Institute of Development, Aging and Cancer, Tohoku University, Sendai 980-8575; Division of Biochemistry, Chiba Cancer Center Research Institute, Chiba 260-8717 [A N.], Japan

The p51/p63 gene is a homologue of p53, the product of which acts as a transcriptional activator by binding to p53-responsive elements in the promoter regions of several p53 downstream genes. Recently, we identified four distinct mutations in the p51/p63 gene after screening >200 human tumors and cell lines. Because all of the detected p51/p63 mutations were missense mutations, the pathogenic effect of these mutations is difficult to determine without performing a functional analysis. In this study, we examined the transcriptional activity of tumor-derived p51/p63 missense mutations using a yeast-based assay and compared the data with that of artificial p51/p63 missense mutations at residues corresponding to the positions and substituted residues of p53 mutation "hotspots." Although most of the p51/p63 missense mutations at the p53 hotspot residues were unable to transactivate the promoters used in this study, the tumor-derived p51/p63 missense mutations retained their ability to transactivate the MDM2 and/or the BAX promoter but not the p21/WAF1 promoter. These results suggest that the p51/p63 mutation might be involved in an unknown tumor suppression pathway distinct from that of p53.

This article has been cited by other articles:

				M.-L. Lu, F. Wikman, T. F. Orntoft, E. Charytonowicz, F. Rabbani, Z. Zhang, G. Dalbagni, K. S. Pohar, G. Yu, and C. Cordon-Cardo Impact of Alterations Affecting the p53 Pathway in Bladder Cancer on Clinical Outcome, Assessed by Conventional and Array-based Methods Clin. Cancer Res., January 1, 2002; 8(1): 171 - 179. [Abstract] [Full Text] [PDF]

				J. A. McGrath, P. H.G. Duijf, V. Doetsch, A. D. Irvine, R. d. Waal, K. R.J. Vanmolkot, V. Wessagowit, A. Kelly, D. J. Atherton, W. A. D. Griffiths, et al. Hay-Wells syndrome is caused by heterozygous missense mutations in the SAM domain of p63 Hum. Mol. Genet., February 1, 2001; 10(3): 221 - 229. [Abstract] [Full Text] [PDF]

				B.-J. Park, S.-J. Lee, J. I. Kim, S.-J. Lee, C.-H. Lee, S.-G. Chang, J.-H. Park, and S.-G. Chi Frequent Alteration of p63 Expression in Human Primary Bladder Carcinomas Cancer Res., July 1, 2000; 60(13): 3370 - 3374. [Abstract] [Full Text]