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Science 8 May 1992:
Vol. 256. no. 5058, pp. 827 - 830
DOI: 10.1126/science.1589764
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Articles

Science, Vol 256, Issue 5058, 827-830
Copyright © 1992 by American Association for the Advancement of Science

articles

Oncogenic forms of p53 inhibit p53-regulated gene expression

SE Kern, JA Pietenpol, S Thiagalingam, A Seymour, KW Kinzler, and B Vogelstein

Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21231.

Mutant forms of the gene encoding the tumor suppressor p53 are found in numerous human malignancies, but the physiologic function of p53 and the effects of mutations on this function are unknown. The p53 protein binds DNA in a sequence-specific manner and thus may regulate gene transcription. Cotransfection experiments showed that wild-type p53 activated the expression of genes adjacent to a p53 DNA binding site. The level of activation correlated with DNA binding in vitro. Oncogenic forms of p53 lost this activity. Moreover, all mutants inhibited the activity of coexpressed wild-type p53, providing a basis for the selection of such mutants during tumorigenesis.


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J. Biol. Chem. 277, 21843-21850
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High-throughput measurement of the Tp53 response to anticancer drugs and random compounds using a stably integrated Tp53-responsive luciferase reporter.
T. A. Sohn, R. Bansal, G. H. Su, K. M. Murphy, and S. E. Kern (2002)
Carcinogenesis 23, 949-958
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Enhancement of p53 activity and inhibition of neural cell proliferation by glucocorticoid receptor activation.
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Induction of Gene Amplification as a Gain-of-Function Phenotype of Mutant p53 Proteins.
S. El-Hizawi, J. P. Lagowski, M. Kulesz-Martin, and A. Albor (2002)
Cancer Res. 62, 3264-3270
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A Role for p53 in Maintaining and Establishing the Quiescence Growth Arrest in Human Cells.
K. Itahana, G. P. Dimri, E. Hara, Y. Itahana, Y. Zou, P.-Y. Desprez, and J. Campisi (2002)
J. Biol. Chem. 277, 18206-18214
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Overexpression of PTEN Increases Sensitivity to SN-38, an Active Metabolite of the Topoisomerase I Inhibitor Irinotecan, in Ovarian Cancer Cells.
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J. A. Livengood, K. E. S. Scoggin, K. Van Orden, S. J. McBryant, R. S. Edayathumangalam, P. J. Laybourn, and J. K. Nyborg (2002)
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W. Fan, S. Jin, T. Tong, H. Zhao, F. Fan, M. J. Antinore, B. Rajasekaran, M. Wu, and Q. Zhan (2002)
J. Biol. Chem. 277, 8061-8067
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M. Cortes-Canteli, M. Pignatelli, A. Santos, and A. Perez-Castillo (2002)
J. Biol. Chem. 277, 5460-5467
   Abstract »    Full Text »    PDF »
Autocrine Interleukin-6 Production in Renal Cell Carcinoma: Evidence for the Involvement of p53.
L. S. Angelo, M. Talpaz, and R. Kurzrock (2002)
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L.-H. Zhang, H.-D. Youn, and J. O. Liu (2001)
J. Biol. Chem. 276, 43534-43540
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J. Gen. Virol. 82, 2235-2241
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AMF1 (GPS2) Modulates p53 Transactivation.
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T. Andreu, C. Ebensperger, E.-M. Westphal, T. Klenner, A. F. Stewart, A. Westhof, P. Muller, R. Knaus, and H. von Melchner (2001)
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M. V. Blagosklonny, P. Giannakakou, L. Y. Romanova, K. M. Ryan, K. H. Vousden, and T. Fojo (2001)
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G. W. Xu, C. L. Nutt, M. C. Zlatescu, M. Keeney, I. Chin-Yee, and J. G. Cairncross (2001)
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E. A. Ratovitski, M. Patturajan, K. Hibi, B. Trink, K. Yamaguchi, and D. Sidransky (2001)
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Genetic Evidence of a Role for ATM in Functional Interaction between Human T-Cell Leukemia Virus Type 1 Tax and p53.
P. L. Van, K.-W. Yim, D.-Y. Jin, G. Dapolito, A. Kurimasa, and K.-T. Jeang (2001)
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Q. Zhu, G. Wani, M. A. Wani, and A. A. Wani (2001)
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RB18A, Whose Gene Is Localized on Chromosome 17q12-q21.1, Regulates in Vivo p53 Transactivating Activity.
R. Frade, M. Balbo, and M. Barel (2000)
Cancer Res. 60, 6585-6589
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Oncogenic Mutations of the p53 Tumor Suppressor: The Demons of the Guardian of the Genome.
A. Sigal and V. Rotter (2000)
Cancer Res. 60, 6788-6793
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A gain of function p53 mutant promotes both genomic instability and cell survival in a novel p53-null mammary epithelial cell model.
K. L. MURPHY, A. P. DENNIS, and J. M. ROSEN (2000)
FASEB J 14, 2291-2302
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p53 from complexity to simplicity: mutant p53 stabilization, gain-of-function, and dominant-negative effect.
M. V. BLAGOSKLONNY (2000)
FASEB J 14, 1901-1907
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Defect in the p53-Mdm2 Autoregulatory Loop Resulting from Inactivation of TAFII250 in Cell Cycle Mutant tsBN462 Cells.
C. Wasylyk and B. Wasylyk (2000)
Mol. Cell. Biol. 20, 5554-5570
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Deregulated Manganese Superoxide Dismutase Expression and Resistance to Oxidative Injury in p53-deficient Cells.
G. Pani, B. Bedogni, R. Anzevino, R. Colavitti, B. Palazzotti, S. Borrello, and T. Galeotti (2000)
Cancer Res. 60, 4654-4660
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Activation of p53 in cervical carcinoma cells by small molecules.
S. Hietanen, S. Lain, E. Krausz, C. Blattner, and D. P. Lane (2000)
PNAS 97, 8501-8506
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Stable expression of Epstein-Barr virus BZLF-1-encoded ZEBRA protein activates p53-dependent transcription in human Jurkat T-lymphoblastoid cells.
D. H. Dreyfus, M. Nagasawa, C. A. Kelleher, and E. W. Gelfand (2000)
Blood 96, 625-634
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p53 Recruitment of CREB Binding Protein Mediated through Phosphorylated CREB: a Novel Pathway of Tumor Suppressor Regulation.
H. A. Giebler, I. Lemasson, and J. K. Nyborg (2000)
Mol. Cell. Biol. 20, 4849-4858
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p53 Regulation of G2 Checkpoint Is Retinoblastoma Protein Dependent.
P. M. Flatt, L. J. Tang, C. D. Scatena, S. T. Szak, and J. A. Pietenpol (2000)
Mol. Cell. Biol. 20, 4210-4223
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Cell cycle inhibition by the anti-angiogenic agent TNP-470 is mediated by p53 and p21WAF1/CIP1.
Y. Zhang, E. C. Griffith, J. Sage, T. Jacks, and J. O. Liu (2000)
PNAS 97, 6427-6432
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A Role for the p38 Mitogen-activated Protein Kinase Pathway in the Transcriptional Activation of p53 on Genotoxic Stress by Chemotherapeutic Agents.
R. Sanchez-Prieto, J. M. Rojas, Y. Taya, and J. S. Gutkind (2000)
Cancer Res. 60, 2464-2472
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Identification of a Sequence Element from p53 That Signals for Mdm2-Targeted Degradation.
J. Gu, D. Chen, J. Rosenblum, R. M. Rubin, and Z.-M. Yuan (2000)
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p53 Mutants Have Selective Dominant-Negative Effects on Apoptosis but Not Growth Arrest in Human Cancer Cell Lines.
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   Abstract »    Full Text »    PDF »
Elevated Expression of Ribosomal Protein Genes L37, RPP-1, and S2 in the Presence of Mutant p53.
W. T. Loging and D. Reisman (1999)
Cancer Epidemiol. Biomarkers Prev. 8, 1011-1016
   Abstract »    Full Text »
Modulation of Cisplatinum Cytotoxicity by p53: Effect of p53-Mediated Apoptosis and DNA Repair.
J. Fan and J. R. Bertino (1999)
Mol. Pharmacol. 56, 966-972
   Abstract »    Full Text »
p53 Negatively Regulates cdc2 Transcription via the CCAAT-binding NF-Y Transcription Factor.
J. Yun, H.-D. Chae, H. E. Choy, J. Chung, H.-S. Yoo, M.-H. Han, and D. Y. Shin (1999)
J. Biol. Chem. 274, 29677-29682
   Abstract »    Full Text »    PDF »
Dominant-Negative Mutations of the Tumor Suppressor p53 Relating to Early Onset of Glioblastoma Multiforme.
M. Marutani, H. Tonoki, M. Tada, M. Takahashi, H. Kashiwazaki, Y. Hida, J.-i. Hamada, M. Asaka, and T. Moriuchi (1999)
Cancer Res. 59, 4765-4769
   Abstract »    Full Text »    PDF »
Binding of p53 to the KIX Domain of CREB Binding Protein. A POTENTIAL LINK TO HUMAN T-CELL LEUKEMIA VIRUS, TYPE I-ASSOCIATED LEUKEMOGENESIS.
K. Van Orden, H. A. Giebler, I. Lemasson, M. Gonzales, and J. K. Nyborg (1999)
J. Biol. Chem. 274, 26321-26328
   Abstract »    Full Text »    PDF »
Multiple Functions of Human Papillomavirus Type 16 E6 Contribute to the Immortalization of Mammary Epithelial Cells.
Y. Liu, J. J. Chen, Q. Gao, S. Dalal, Y. Hong, C. P. Mansur, V. Band, and E. J. Androphy (1999)
J. Virol. 73, 7297-7307
   Abstract »    Full Text »
High Frequency and Heterogeneous Distribution of p53 Mutations in Aflatoxin B1-induced Mouse Lung Tumors.
A. S. Tam, J. F. Foley, T. R. Devereux, R. R. Maronpot, and T. E. Massey (1999)
Cancer Res. 59, 3634-3640
   Abstract »    Full Text »    PDF »
Activation of p53 Function in Carcinoma Cells by the alpha 6beta 4 Integrin.
R. E. Bachelder, A. Marchetti, R. Falcioni, S. Soddu, and A. M. Mercurio (1999)
J. Biol. Chem. 274, 20733-20737
   Abstract »    Full Text »    PDF »
Oligomerization Is Required for p53 to be Efficiently Ubiquitinated by MDM2.
C. G. Maki (1999)
J. Biol. Chem. 274, 16531-16535
   Abstract »    Full Text »    PDF »
Reactivation of Mutant p53 through Interaction of a C-Terminal Peptide with the Core Domain.
G. Selivanova, L. Ryabchenko, E. Jansson, V. Iotsova, and K. G. Wiman (1999)
Mol. Cell. Biol. 19, 3395-3402
   Abstract »    Full Text »    PDF »
p53 Is a Transcriptional Activator of the Muscle-specific Phosphoglycerate Mutase Gene and Contributesin Vivo to the Control of Its Cardiac Expression.
P. Ruiz-Lozano, M. L. Hixon, M. W. Wagner, A. I. Flores, S. Ikawa, A. S. Baldwin Jr., K. R. Chien, and A. Gualberto (1999)
Cell Growth Differ. 10, 295-306
   Abstract »    Full Text »
Two Polymorphic Variants of Wild-Type p53 Differ Biochemically and Biologically.
M. Thomas, A. Kalita, S. Labrecque, D. Pim, L. Banks, and G. Matlashewski (1999)
Mol. Cell. Biol. 19, 1092-1100
   Abstract »    Full Text »    PDF »
p73 Function Is Inhibited by Tumor-Derived p53 Mutants in Mammalian Cells.
C. J. Di Como, C. Gaiddon, and C. Prives (1999)
Mol. Cell. Biol. 19, 1438-1449
   Abstract »    Full Text »    PDF »


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