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Science 31 August 1990:
Vol. 249. no. 4972, pp. 1046 - 1049
DOI: 10.1126/science.2144363
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Articles

Science, Vol 249, Issue 4972, 1046-1049
Copyright © 1990 by American Association for the Advancement of Science

articles

Presence of a potent transcription activating sequence in the p53 protein

S Fields and SK Jang

Department of Microbiology, School of Medicine, State University of New York, Stony Brook 11794.

The p53 gene is frequently mutated in a wide variety of human cancers. However, the role of the wild-type p53 gene in growth control is not known. Hybrid proteins that contain the DNA binding domain of yeast GAL4 and portions of p53 have been used to show that the p53 protein contains a transcription-activating sequence that functions in both yeast and mammalian cells. The NH2-terminal 73 residues of p53 activated transcription in mammalian cells as efficiently as the herpes virus protein VP16, which contains one of the strongest known activation domains. Combined with previous data that showed p53 is localized to the nucleus and can bind to DNA, these results support the idea that one function of p53 is to activate the transcription of genes that suppress cell proliferation.


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Hsp90 Regulates the Activity of Wild Type p53 under Physiological and Elevated Temperatures.
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TAFII70 Isoform-Specific Growth Suppression Correlates With Its Ability to Complex With the GADD45a Protein.
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The Proteasome Inhibitor Bortezomib Stabilizes a Novel Active Form of p53 in Human LNCaP-Pro5 Prostate Cancer Cells.
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DNA-dependent Acetylation of p53 by the Transcription Coactivator p300.
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J. Gen. Virol. 84, 897-906
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Studies of the Mechanism of Transactivation of the Adeno-Associated Virus p19 Promoter by Rep Protein.
D. F. Lackner and N. Muzyczka (2002)
J. Virol. 76, 8225-8235
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The yeast protein Xtc1 functions as a direct transcriptional repressor.
A. Traven, L. Staresincic, M. Arneric, and M. Sopta (2002)
Nucleic Acids Res. 30, 2358-2364
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PTEN Protects p53 from Mdm2 and Sensitizes Cancer Cells to Chemotherapy.
L. D. Mayo, J. E. Dixon, D. L. Durden, N. K. Tonks, and D. B. Donner (2002)
J. Biol. Chem. 277, 5484-5489
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Analysis of p53-regulated gene expression patterns using oligonucleotide arrays.
R. Zhao, K. Gish, M. Murphy, Y. Yin, D. Notterman, W. H. Hoffman, E. Tom, D. H. Mack, and A. J. Levine (2000)
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The N-Terminal Domain of p73 Interacts with the CH1 Domain of p300/CREB Binding Protein and Mediates Transcriptional Activation and Apoptosis.
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Identification and classification of p53-regulated genes.
J. Yu, L. Zhang, P. M. Hwang, C. Rago, K. W. Kinzler, and B. Vogelstein (1999)
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One Mechanism for Cell Type-specific Regulation of the bax Promoter by the Tumor Suppressor p53 Is Dictated by the p53 Response Element.
E. C. Thornborrow and J. J. Manfredi (1999)
J. Biol. Chem. 274, 33747-33756
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Molecular Evolution of the Thermosensitive PAb1620 Epitope of Human p53 by DNA Shuffling.
D. P. Xirodimas and D. P. Lane (1999)
J. Biol. Chem. 274, 28042-28049
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Physical Interaction and Functional Antagonism between the RNA Polymerase II Elongation Factor ELL and p53.
N. Shinobu, T. Maeda, T. Aso, T. Ito, T. Kondo, K. Koike, and M. Hatakeyama (1999)
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Inhibition of hTAFII32-binding Implicated in the Transcriptional Repression by Central Regions of Mutant p53 Proteins.
S.-F. Tung, J.-Y. Chuang, C.-T. Lin, M.-Y. Lai, C.-W. Wu, and Y.-S. Lin (1999)
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p53 Sites Acetylated In Vitro by PCAF and p300 Are Acetylated In Vivo in Response to DNA Damage.
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Proliferative and Apoptotic Responses in Cancers With Special Reference To Oral Cancers.
A.R. Kamer, L. Krebs, S.A. Hoghooghi, and C. Liebow (1999)
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Stimulation of p53-mediated Transcriptional Activation by the p53-binding Proteins, 53BP1 and 53BP2.
K. Iwabuchi, B. Li, H. F. Massa, B. J. Trask, T. Date, and S. Fields (1998)
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Non-p53 p53RE binding protein, a human transcription factor functionally analogous to P53.
X. Zeng, A. J. Levine, and H. Lu (1998)
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Identification of an additional negative regulatory region for p53 sequence-specific DNA binding.
B. F. Muller-Tiemann, T. D. Halazonetis, and J. J. Elting (1998)
PNAS 95, 6079-6084
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A cofactor, TIP30, specifically enhances HIV-1 Tatactivated transcription.
H. Xiao, Y. Tao, J. Greenblatt, and R. G. Roeder (1998)
PNAS 95, 2146-2151
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Identification of a Novel Transcriptional Regulatory Element Common to the p53 and Interferon Regulatory Factor 1 Genes.
C. Lallemand, M. Bayat-Sarmadi, B. Blanchard, and M. G. Tovey (1997)
J. Biol. Chem. 272, 29801-29809
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Glucose Catabolism in Cancer Cells. THE TYPE II HEXOKINASE PROMOTER CONTAINS FUNCTIONALLY ACTIVE RESPONSE ELEMENTS FOR THE TUMOR SUPPRESSOR p53.
S. P. Mathupala, C. Heese, and P. L. Pedersen (1997)
J. Biol. Chem. 272, 22776-22780
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HSP70 Binding Sites in the Tumor Suppressor Protein p53.
A. M. Fourie, T. R. Hupp, D. P. Lane, B.-C. Sang, M. S. Barbosa, J. F. Sambrook, and M.-J. H. Gething (1997)
J. Biol. Chem. 272, 19471-19479
   Abstract »    Full Text »    PDF »
Repression of p53-mediated transcription by MDM2: a dual mechanism.
C. J. Thut, J. A. Goodrich, and R. Tjian (1997)
Genes & Dev. 11, 1974-1986
   Abstract »    Full Text »    PDF »
Co-localization of Endogenous and Exogenous p53 Proteins in Nasopharyngeal Carcinoma Cells.
J.-K. Hwang and C.-T. Lin (1997)
J. Histochem. Cytochem. 45, 991-1004
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Inhibition of Protein Phosphatase Activity Induces p53-dependent Apoptosis in the Absence of p53 Transactivation.
Y. Yan, J. W. Shay, W. E. Wright, and M. C. Mumby (1997)
J. Biol. Chem. 272, 15220-15226
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Proteasome- and p53-dependent Masking of Signal Transducer and Activator of Transcription (STAT) Factors.
R. J. Rayanade, K. Patel, M. Ndubuisi, S. Sharma, S. Omura, J. D. Etlinger, R. Pine, and P. B. Sehgal (1997)
J. Biol. Chem. 272, 4659-4662
   Abstract »    Full Text »    PDF »
Identification of a novel p53 functional domain that is necessary for efficient growth suppression.
K. K. Walker and A. J. Levine (1996)
PNAS 93, 15335-15340
   Abstract »    Full Text »    PDF »
p53 and Breast Cancer.
P. Robbins (1996)
International Journal of Surgical Pathology 4, 93-110
   Abstract »    PDF »
p53 Stimulates Promoter Activity of the sgk Serum/Glucocorticoid-inducible Serine/Threonine Protein Kinase Gene in Rodent Mammary Epithelial Cells.
A. C. Maiyar, A. J. Huang, P. T. Phu, H. H. Cha, and G. L. Firestone (1996)
J. Biol. Chem. 271, 12414-12422
   Abstract »    Full Text »    PDF »
The XPB and XPD DNA helicases are components of the p53-mediated apoptosis pathway..
X W Wang, W Vermeulen, J D Coursen, M Gibson, S E Lupold, K Forrester, G Xu, L Elmore, H Yeh, J H Hoeijmakers, et al. (1996)
Genes & Dev. 10, 1219-1232
   Abstract »    PDF »
Allosteric Regulation of the Thermostability and DNA Binding Activity of Human p53 by Specific Interacting Proteins.
S. Hansen, T. R. Hupp, and D. P. Lane (1996)
J. Biol. Chem. 271, 3917-3924
   Abstract »    Full Text »    PDF »
Transactivation Ability of p53 Transcriptional Activation Domain Is Directly Related to the Binding Affinity to TATA-binding Protein.
J. Chang, D.-H. Kim, S. W. Lee, K. Y. Choi, and Y. C. Sung (1995)
J. Biol. Chem. 270, 25014-25019
   Abstract »    Full Text »    PDF »
Suppression of the Yeast Mutation rft1-1 by Human p53.
A. Koerte, T. Chong, X. Li, K. Wahane, and M. Cai (1995)
J. Biol. Chem. 270, 22556-22564
   Abstract »    Full Text »    PDF »
Crystal structure of the tetramerization domain of the p53 tumor suppressor at 1.7 angstroms.
P. Jeffrey, S Gorina, and N. Pavletich (1995)
Science 267, 1498-1502
   Abstract »    PDF »
p53 transcriptional activation mediated by coactivators TAFII40 and TAFII60.
C. Thut, J. Chen, R Klemm, and R Tjian (1995)
Science 267, 100-104
   Abstract »    PDF »
Crystal structure of a p53 tumor suppressor-DNA complex: understanding tumorigenic mutations.
Y Cho, S Gorina, P. Jeffrey, and N. Pavletich (1994)
Science 265, 346-355
   Abstract »    PDF »
Several hydrophobic amino acids in the p53 amino-terminal domain are required for transcriptional activation, binding to mdm-2 and the adenovirus 5 E1B 55-kD protein..
J Lin, J Chen, B Elenbaas, and A J Levine (1994)
Genes & Dev. 8, 1235-1246
   Abstract »    PDF »
Regulation of the Cryptic Sequence-specific DNA-binding Function of p53 by Protein Kinases.
T.R. Hupp and D.P. Lane (1994)
Cold Spring Harb Symp Quant Biol 59, 195-206
   Abstract »    PDF »
Functions of the p53 Protein in Growth Regulation and Tumor Suppression.
J. Lin, X. Wu, J. Chen, A. Chang, and A.J. Levine (1994)
Cold Spring Harb Symp Quant Biol 59, 215-223
   Abstract »    PDF »
Control of p53-dependent Apoptosis by E1B, Bcl-2, and Ha-ras Proteins.
E. White, S.-K. Chiou, L. Rao, P. Sabbatini, and H.-J. Lin (1994)
Cold Spring Harb Symp Quant Biol 59, 395-402
   Abstract »    PDF »
The DNA-binding domain of p53 contains the four conserved regions and the major mutation hot spots..
N P Pavletich, K A Chambers, and C O Pabo (1993)
Genes & Dev. 7, 2556-2564
   Abstract »    PDF »
A proteolytic fragment from the central region of p53 has marked sequence-specific DNA-binding activity when generated from wild-type but not from oncogenic mutant p53 protein..
J Bargonetti, J J Manfredi, X Chen, D R Marshak, and C Prives (1993)
Genes & Dev. 7, 2565-2574
   Abstract »    PDF »
p53 domains: identification and characterization of two autonomous DNA-binding regions..
Y Wang, M Reed, P Wang, J E Stenger, G Mayr, M E Anderson, J F Schwedes, and P Tegtmeyer (1993)
Genes & Dev. 7, 2575-2586
   Abstract »    PDF »
The p53-mdm-2 autoregulatory feedback loop..
X Wu, J H Bayle, D Olson, and A J Levine (1993)
Genes & Dev. 7, 1126-1132
   Abstract »    PDF »
The retinoblastoma protein associates with the protein phosphatase type 1 catalytic subunit..
T Durfee, K Becherer, P L Chen, S H Yeh, Y Yang, A E Kilburn, W H Lee, and S J Elledge (1993)
Genes & Dev. 7, 555-569
   Abstract »    PDF »
Regulation of the human hsp70 promoter by p53.
S. Agoff, J Hou, D. Linzer, and B Wu (1993)
Science 259, 84-87
   Abstract »    PDF »
Site-specific binding of wild-type p53 to cellular DNA is inhibited by SV40 T antigen and mutant p53..
J Bargonetti, I Reynisdottir, P N Friedman, and C Prives (1992)
Genes & Dev. 6, 1886-1898
   Abstract »    PDF »
Malignant transformation by a mutant of the IFN-inducible dsRNA-dependent protein kinase.
A. Koromilas, S Roy, G. Barber, M. Katze, and N Sonenberg (1992)
Science 257, 1685-1689
   Abstract »    PDF »
Wild-type p53 mediates positive regulation of gene expression through a specific DNA sequence element..
G P Zambetti, J Bargonetti, K Walker, C Prives, and A J Levine (1992)
Genes & Dev. 6, 1143-1152
   Abstract »    PDF »
Oncogenic forms of p53 inhibit p53-regulated gene expression.
S. Kern, J. Pietenpol, S Thiagalingam, A Seymour, K. Kinzler, and B Vogelstein (1992)
Science 256, 827-830
   Abstract »    PDF »
Modulation of activity of the promoter of the human MDR1 gene by Ras and p53.
K. Chin, K Ueda, I Pastan, and M. Gottesman (1992)
Science 255, 459-462
   Abstract »    PDF »
Tumor suppressor genes.
R. Weinberg (1991)
Science 254, 1138-1146
   Abstract »    PDF »
Transcriptional repression mediated by the WT1 Wilms tumor gene product.
S. Madden, D. Cook, J. Morris, A Gashler, V. Sukhatme, and F. Rauscher III (1991)
Science 253, 1550-1553
   Abstract »    PDF »
p53 mutations in human cancers.
M Hollstein, D Sidransky, B Vogelstein, and C. Harris (1991)
Science 253, 49-53
   Abstract »    PDF »
Identification of p53 as a sequence-specific DNA-binding protein.
S. Kern, K. Kinzler, A Bruskin, D Jarosz, P Friedman, C Prives, and B Vogelstein (1991)
Science 252, 1708-1711
   Abstract »    PDF »
Regulation of Transformation and the Cell Cycle by p53.
G.P. Zambetti, R.S. Quartin, J. Martinez, I. Georgoff, J. Momand, D. Dittmer, C.A. Finlay, and A.J. Levine (1991)
Cold Spring Harb Symp Quant Biol 56, 219-225
   Abstract »    PDF »
Functional Consequences of the Interactions of the p53 Tumor Suppressor Protein and SV40 Large Tumor Antigen.
C. Prives, J. Bargonetti, P.N. Friedman, J.J. Manfredi, and E.H. Wang (1991)
Cold Spring Harb Symp Quant Biol 56, 227-235
   Abstract »    PDF »
Local Structural Elements in the Mostly Unstructured Transcriptional Activation Domain of Human p53.
H. Lee, K. H. Mok, R. Muhandiram, K.-H. Park, J.-E. Suk, D.-H. Kim, J. Chang, Y. C. Sung, K. Y. Choi, and K.-H. Han (2000)
J. Biol. Chem. 275, 29426-29432
   Abstract »    Full Text »    PDF »
p53 Amino Acids 339-346 Represent the Minimal p53 Repression Domain.
T.-M. Hong, J. J. W. Chen, K. Peck, P.-C. Yang, and C.-W. Wu (2001)
J. Biol. Chem. 276, 1510-1515
   Abstract »    Full Text »    PDF »
The Tumor Suppressor Protein p53 Requires a Cofactor to Activate Transcriptionally the Human BAX Promoter.
E. C. Thornborrow and J. J. Manfredi (2001)
J. Biol. Chem. 276, 15598-15608
   Abstract »    Full Text »    PDF »
Functional overlap of sequences that activate transcription and signal ubiquitin-mediated proteolysis.
S. E. Salghetti, M. Muratani, H. Wijnen, B. Futcher, and W. P. Tansey (2000)
PNAS 97, 3118-3123
   Abstract »    Full Text »    PDF »
Histone deacetylase-dependent transcriptional repression by pRB in yeast occurs independently of interaction through the LXCXE binding cleft.
B. K. Kennedy, O. W. Liu, F. A. Dick, N. Dyson, E. Harlow, and M. Vidal (2001)
PNAS 98, 8720-8725
   Abstract »    Full Text »    PDF »


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