| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Advances in Brief |
Np63
and TAp63 Regulate Transcription of Genes with Distinct Biological Functions in Cancer and Development1
Departments of Otolaryngology-Head and Neck Surgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205-2196 [G. W., S. N., M. H., M. O., C-C. R. L., S. M. D., Z. G., N. B., Y. C., P. R., J. C., C. M., D. S., B. T.]; Laboratory of Population Genetics, National Cancer Institute, Rockville, Maryland [T. D., J. J.]; and Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205-2196 [E. R.]
The p63 gene shows remarkable structural similarity to the p53 and p73 genes. Because of two promoters, the p63 gene generates two types of protein isoforms, TAp63 and 
Np63. Each type yields three isotypes (
, ß, 
) because of differential splicing of the p63 COOH terminus. The purpose of this study was to determine whether there is a functional link between the distinct p63 isotypes in their transcriptional regulation of downstream targets and their role in various cellular functions. TAp63 and Np63 adenovirus expression vectors were introduced into Saos2 cells for 4 and 24 h, and then gene profiling was performed using a DNA microarray chip analysis. Seventy-four genes (>2-fold change in expression) were identified that overlapped between two independent studies. Thirty-five genes were selected for direct expression testing of which 27 were confirmed by reverse transcription-PCR or Northern blot analysis. A survey of these genes shows that p63 can regulate a wide range of downstream gene targets with various cellular functions, including cell cycle control, stress, and signal transduction. Our study thus revealed p63 transcriptional regulation of many genes in cancer and development while often demonstrating opposing regulatory functions for TAp63 and Np63.
This article has been cited by other articles:
|
|
 |
|
  Y. Li, M. J. Peart, and C. Prives Stxbp4 Regulates {Delta}Np63 Stability by Suppression of RACK1-Dependent Degradation Mol. Cell. Biol., July 15, 2009; 29(14): 3953 - 3963. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. E. King, R. M. Ponnamperuma, C. Allen, H. Lu, P. Duggal, Z. Chen, C. Van Waes, and W. C. Weinberg The p53 Homologue {Delta}Np63{alpha} Interacts with the Nuclear Factor-{kappa}B Pathway to Modulate Epithelial Cell Growth Cancer Res., July 1, 2008; 68(13): 5122 - 5131. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Lantner, D. Starlets, Y. Gore, L. Flaishon, A. Yamit-Hezi, R. Dikstein, L. Leng, R. Bucala, Y. Machluf, M. Oren, et al. CD74 induces TAp63 expression leading to B-cell survival Blood, December 15, 2007; 110(13): 4303 - 4311. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. S. Sayan, A. E. Sayan, A. L. Yang, R. I. Aqeilan, E. Candi, G. M. Cohen, R. A. Knight, C. M. Croce, and G. Melino Cleavage of the transactivation-inhibitory domain of p63 by caspases enhances apoptosis PNAS, June 26, 2007; 104(26): 10871 - 10876. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Candi, A. Terrinoni, A. Rufini, A. Chikh, A. M. Lena, Y. Suzuki, B. S. Sayan, R. A. Knight, and G. Melino p63 is upstream of IKK{alpha} in epidermal development J. Cell Sci., November 15, 2006; 119(22): 4617 - 4622. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. B. Truong, M. Kretz, T. W. Ridky, R. Kimmel, and P. A. Khavari p63 regulates proliferation and differentiation of developmentally mature keratinocytes. Genes & Dev., November 15, 2006; 20(22): 3185 - 3197. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. M. Caserta, R. Kommagani, Z. Yuan, D. J. Robbins, C. A. Mercer, and M. P. Kadakia p63 Overexpression Induces the Expression of Sonic Hedgehog Mol. Cancer Res., October 1, 2006; 4(10): 759 - 768. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Rossi, R. I. Aqeilan, M. Neale, E. Candi, P. Salomoni, R. A. Knight, C. M. Croce, and G. Melino The E3 ubiquitin ligase Itch controls the protein stability of p63 PNAS, August 22, 2006; 103(34): 12753 - 12758. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. M. Keyes, H. Vogel, M. I. Koster, X. Guo, Y. Qi, K. M. Petherbridge, D. R. Roop, A. Bradley, and A. A. Mills p63 heterozygous mutant mice are not prone to spontaneous or chemically induced tumors PNAS, May 30, 2006; 103(22): 8435 - 8440. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Antonini, B. Rossi, R. Han, A. Minichiello, T. Di Palma, M. Corrado, S. Banfi, M. Zannini, J. L. Brissette, and C. Missero An Autoregulatory Loop Directs the Tissue-Specific Expression of p63 through a Long-Range Evolutionarily Conserved Enhancer Mol. Cell. Biol., April 15, 2006; 26(8): 3308 - 3318. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B.-C. Nguyen, K. Lefort, A. Mandinova, D. Antonini, V. Devgan, G. Della Gatta, M. I. Koster, Z. Zhang, J. Wang, A. T. di Vignano, et al. Cross-regulation between Notch and p63 in keratinocyte commitment to differentiation Genes & Dev., April 15, 2006; 20(8): 1028 - 1042. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Laurikkala, M. L. Mikkola, M. James, M. Tummers, A. A. Mills, and I. Thesleff p63 regulates multiple signalling pathways required for ectodermal organogenesis and differentiation Development, April 15, 2006; 133(8): 1553 - 1563. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Testoni and R. Mantovani Mechanisms of transcriptional repression of cell-cycle G2/M promoters by p63 Nucleic Acids Res., February 9, 2006; 34(3): 928 - 938. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K.E. King, R.M. Ponnamperuma, M.J. Gerdes, T. Tokino, T. Yamashita, C.C. Baker, and W.C. Weinberg Unique domain functions of p63 isotypes that differentially regulate distinct aspects of epidermal homeostasis Carcinogenesis, January 1, 2006; 27(1): 53 - 63. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-C. Bourdon, K. Fernandes, F. Murray-Zmijewski, G. Liu, A. Diot, D. P. Xirodimas, M. K. Saville, and D. P. Lane p53 isoforms can regulate p53 transcriptional activity Genes & Dev., September 15, 2005; 19(18): 2122 - 2137. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. M. Keyes, Y. Wu, H. Vogel, X. Guo, S. W. Lowe, and A. A. Mills p63 deficiency activates a program of cellular senescence and leads to accelerated aging Genes & Dev., September 1, 2005; 19(17): 1986 - 1999. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. MacPartlin, S. Zeng, H. Lee, D. Stauffer, Y. Jin, M. Thayer, and H. Lu p300 Regulates p63 Transcriptional Activity J. Biol. Chem., August 26, 2005; 280(34): 30604 - 30610. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. A. Johnson, E. M. Shepard, and K. W. Scotto Differential Regulation of MDR1 Transcription by the p53 Family Members: ROLE OF THE DNA BINDING DOMAIN J. Biol. Chem., April 8, 2005; 280(14): 13213 - 13219. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. A. Moreira, G. Ohlsson, F. E. Rank, and J. E. Celis Down-regulation of the Tumor Suppressor Protein 14-3-3{sigma} Is a Sporadic Event in Cancer of the Breast Mol. Cell. Proteomics, April 1, 2005; 4(4): 555 - 569. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. E. Barbieri, C. A. Perez, K. N. Johnson, K. A. Ely, D. Billheimer, and J. A. Pietenpol IGFBP-3 Is a Direct Target of Transcriptional Regulation by {Delta}Np63{alpha} in Squamous Epithelium Cancer Res., March 15, 2005; 65(6): 2314 - 2320. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Wu, M. Osada, Z. Guo, A. Fomenkov, S. Begum, M. Zhao, S. Upadhyay, M. Xing, F. Wu, C. Moon, et al. {Delta}Np63{alpha} Up-Regulates the Hsp70 Gene in Human Cancer Cancer Res., February 1, 2005; 65(3): 758 - 766. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Teuliere, M. M. Faraldo, M.-A. Deugnier, M. Shtutman, A. Ben-Ze'ev, J. P. Thiery, and M. A. Glukhova Targeted activation of {beta}-catenin signaling in basal mammary epithelial cells affects mammary development and leads to hyperplasia Development, January 15, 2005; 132(2): 267 - 277. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. A. Moreira, P. Gromov, and J. E. Celis Expression of the Tumor Suppressor Protein 14-3-3{sigma} Is Down-regulated in Invasive Transitional Cell Carcinomas of the Urinary Bladder Undergoing Epithelial-to-Mesenchymal Transition Mol. Cell. Proteomics, April 1, 2004; 3(4): 410 - 419. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. I. Koster, S. Kim, A. A. Mills, F. J. DeMayo, and D. R. Roop p63 is the molecular switch for initiation of an epithelial stratification program Genes & Dev., January 15, 2004; 18(2): 126 - 131. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 U. M. Moll The Role of p63 and p73 in Tumor Formation and Progression: Coming of Age Toward Clinical Usefulness: Commentary re: F. Koga et al., Impaired p63 Expression Associates with Poor Prognosis and Uroplakin III Expression in Invasive Urothelial Carcinoma of the Bladder. Clin. Cancer Res., 9: 5501-5507, 2003, and P. Puig et al., p73 Expression in Human Normal and Tumor Tissues: Loss of p73{alpha} Expression Is Associated with Tumor Progression in Bladder Cancer. Clin. Cancer Res., 9: 5642-5651, 2003. Clin. Cancer Res., November 15, 2003; 9(15): 5437 - 5441. [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
