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| p53SummaryGene Symbol: p53 Description: tumor protein p53 Alias: BCC7, LFS1, P53, TRP53, antigen NY-CO-13, cellular tumor antigen p53, p53 tumor suppressor, phosphoprotein p53, transformation-related protein 53 Species: human Top Publications
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Dual-site regulation of MDM2 E3-ubiquitin ligase activityMaura Wallace
CRUK Interferon and Cell Signalling Group, University of Edinburgh Cancer Research Centre, Crewe Road South, Edinburgh EH4 2XR, United Kingdom
Mol Cell 23:251-63. 2006The control of p53 ubiquitination by MDM2 provides a model system to define how an E3-ligase functions on a conformationally flexible substrate...
p53 polymorphisms: cancer implicationsCatherine Whibley
Leeds Institute of Genetics, Health and Therapeutics, LIGHT Laboratories, University of Leeds, Leeds, LS2 9JT, UK
Nat Rev Cancer 9:95-107. 2009The normal functioning of p53 is a potent barrier to cancer...
Ultraslow oligomerization equilibria of p53 and its implicationsEviatar Natan
Medical Research Council Centre for Protein Engineering, Cambridge CB2 0QH, United Kingdom
Proc Natl Acad Sci U S A 106:14327-32. 2009The tumor suppressor p53 is in equilibrium at cellular concentrations between dimers and tetramers. Oncogenic mutant p53 (mut) exerts a dominant-negative effect on co-expression of p53 wild-type (wt) and mut alleles in cancer cells...
Transactivation of miR-34a by p53 broadly influences gene expression and promotes apoptosisTsung Cheng Chang
The McKusick Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Mol Cell 26:745-52. 2007The p53 tumor suppressor protein is a critical regulator of the cellular response to cancer-initiating insults such as genotoxic stress...
Transcriptional activation of miR-34a contributes to p53-mediated apoptosisNina Raver-Shapira
Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot 76100, Israel
Mol Cell 26:731-43. 2007b>p53 is a potent tumor suppressor, whose biological effects are largely due to its function as a transcriptional regulator...
Blinded by the Light: The Growing Complexity of p53Karen H Vousden
The Beatson Institute for Cancer Research, Garscube Estate, Glasgow, UK
Cell 137:413-31. 2009While the tumor suppressor functions of p53 have long been recognized, the contribution of p53 to numerous other aspects of disease and normal life is only now being appreciated...
Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4aM Serrano
Cold Spring Harbor Laboratory, New York 11724, USA
Cell 88:593-602. 1997..of primary cells by ras requires either a cooperating oncogene or the inactivation of tumor suppressors such as p53 or p16...
Activation of p53 sequence-specific DNA binding by acetylation of the p53 C-terminal domainW Gu
Laboratory of Biochemistry and Molecular Biology, The Rockefeller University, New York, New York 10021, USA
Cell 90:595-606. 1997The tumor suppressor p53 exerts antiproliferation effects through its ability to function as a sequence-specific DNA-binding transcription factor. Here, we demonstrate that p53 can be modified by acetylation both in vivo and in vitro...
p53-mediated activation of miRNA34 candidate tumor-suppressor genesGuido T Bommer
Department of Internal Medicine, University of Michigan School of Medicine, Ann Arbor, MI 48109 2200, USA
Curr Biol 17:1298-307. 2007In response to varied cell stress signals, the p53 tumor-suppressor protein activates a multitude of genes encoding proteins with functions in cell-cycle control, DNA repair, senescence, and apoptosis...
Differential regulation of microRNAs by p53 revealed by massively parallel sequencing: miR-34a is a p53 target that induces apoptosis and G1-arrestValery Tarasov
Molecular Oncology, Max Planck Institute of Biochemistry, Am Klopferspitz 18, D 82152 Martinsried, Germany
Cell Cycle 6:1586-93. 2007In a genome-wide screen for microRNAs regulated by the transcription factor encoded by the p53 tumor suppressor gene we found that after p53-activation the abundance of thirty-four miRNAs was significantly increased, whereas sixteen ..
p53 has a direct apoptogenic role at the mitochondriaMotohiro Mihara
Department of Pathology, Stony Brook University, Stony Brook, NY 11794, USA
Mol Cell 11:577-90. 2003b>p53 induces apoptosis by target gene regulation and transcription-independent signaling. However, a mechanism for the latter was unknown...
Paradoxical suppression of cellular senescence by p53Zoya N Demidenko
Department of Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA
Proc Natl Acad Sci U S A 107:9660-4. 2010The tumor suppressor p53 is a canonical inducer of cellular senescence (irreversible loss of proliferative potential and senescent morphology)...
p53 mutations in human cancersM Hollstein
Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892
Science 253:49-53. 1991Mutations in the evolutionarily conserved codons of the p53 tumor suppressor gene are common in diverse types of human cancer...
Tip60-dependent acetylation of p53 modulates the decision between cell-cycle arrest and apoptosisYi Tang
Institute for Cancer Genetics, Surgeons, Columbia University, 1150 St Nicholas Ave, New York, New York 10032, USA
Mol Cell 24:827-39. 2006Upon DNA damage and other types of stress, p53 induces either cell-cycle arrest or apoptosis depending on the cellular context...
Germ line p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasmsD Malkin
Division of Molecular Genetics, Massachusetts General Hospital Cancer Center, Charlestown 02129
Science 250:1233-8. 1990..The alternative approach was to select the most plausible candidate gene. The tumor suppressor gene, p53, was studied because of previous indications that this gene is inactivated in the sporadic (nonfamilial) forms of ..
Mutant p53 gain-of-function in cancerMoshe Oren
Department of Molecular Cell Biology, The Weizmann Institute, Rehovot 76100, Israel
Cold Spring Harb Perspect Biol 2:a001107. 2010In its wild-type form, p53 is a major tumor suppressor whose function is critical for protection against cancer. Many human tumors carry missense mutations in the TP53 gene, encoding p53...
Mono- versus polyubiquitination: differential control of p53 fate by Mdm2Muyang Li
Institute for Cancer Genetics and Department of Pathology, College of Physicians and Surgeons, Columbia University, 1150 St Nicholas Avenue, New York, NY 10032, USA
Science 302:1972-5. 2003Although Mdm2-mediated ubiquitination is essential for both degradation and nuclear export of p53, the molecular basis for the differential effects of Mdm2 remains unknown...
P53-induced microRNA-107 inhibits HIF-1 and tumor angiogenesisMunekazu Yamakuchi
Department of Medicine, Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA
Proc Natl Acad Sci U S A 107:6334-9. 2010..Here we show that p53 regulates hypoxic signaling through the transcriptional regulation of microRNA-107 (miR-107)...
TP53 mutations in human cancers: functional selection and impact on cancer prognosis and outcomesA Petitjean
International Agency for Research on Cancer, Lyon, France
Oncogene 26:2157-65. 2007..New data on mutant p53 protein function, cancer phenotype and prognosis have recently been integrated in the International Agency for ..
Direct activation of Bax by p53 mediates mitochondrial membrane permeabilization and apoptosisJerry E Chipuk
Division of Cellular Immunology, La Jolla Institute for Allergy and Immunology, 10355 Science Center Drive, San Diego, CA 92121, USA
Science 303:1010-4. 2004The tumor suppressor p53 exerts its anti-neoplastic activity primarily through the induction of apoptosis...
Acetylation of the p53 DNA-binding domain regulates apoptosis inductionStephen M Sykes
Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA
Mol Cell 24:841-51. 2006The ability of p53 to induce apoptosis plays an important role in tumor suppression. Here, we describe a previously unknown posttranslational modification of the DNA-binding domain of p53...
Regulation of p53 activity by its interaction with homeodomain-interacting protein kinase-2Thomas G Hofmann
Division of Immunochemistry G0200 German Cancer Research Center DKFZ, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany
Nat Cell Biol 4:1-10. 2002Transcriptional activity of p53, a central regulatory switch in a network controlling cell proliferation and apoptosis, is modulated by protein stability and post-translational modifications including phosphorylation and acetylation...
p53 post-translational modification: deregulated in tumorigenesisChao Dai
Institute for Cancer Genetics, College of Physicians and Surgeons, Columbia University, 1130 St Nicholas Avenue, New York, NY 10032, USA
Trends Mol Med 16:528-36. 2010The p53 tumor suppressor protein has well-established roles in monitoring various types of stress signals by activating specific transcriptional targets that control cell cycle arrest and apoptosis, although some activities are also ..
p53 regulates epithelial-mesenchymal transition and stem cell properties through modulating miRNAsChun Ju Chang
Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Nat Cell Biol 13:317-23. 2011..Here, using genomic approaches, we show that tumour suppressor p53 has a role in regulating both EMT and EMT-associated stem cell properties through transcriptional activation of the ..
Homeodomain-interacting protein kinase-2 phosphorylates p53 at Ser 46 and mediates apoptosisGabriella D'Orazi
Molecular Oncogenesis Laboratory, Regina Elena Cancer Institute, Via delle Messi d Oro 156, 00158 Rome, Italy
Nat Cell Biol 4:11-9. 2002Phosphorylation of p53 at Ser 46 was shown to regulate p53 apoptotic activity...
TP53 mutations and survival in squamous-cell carcinoma of the head and neckM Luana Poeta
Johns Hopkins University, Baltimore, MD 21287, USA
N Engl J Med 357:2552-61. 2007The abrogation of function of the tumor-suppressor protein p53 as a result of mutation of its gene, TP53, is one of the most common genetic alterations in cancer cells...
Acetylation of p53 activates transcription through recruitment of coactivators/histone acetyltransferasesN A Barlev
Molecular Genetics Program, The Wistar Institute, Philadelphia, PA 19104, USA
Mol Cell 8:1243-54. 2001Cellular DNA damage causes stabilization and activation of the tumor suppressor and transcription factor p53, in part by promoting multiple covalent modifications of the p53 protein, including acetylation...
Modulation of microRNA processing by p53Hiroshi I Suzuki
Department of Molecular Pathology, Graduate School of Medicine, University of Tokyo, 7 3 1 Hongo, Bunkyo ku, Tokyo 113 0033, Japan
Nature 460:529-33. 2009..Here we show that a central tumour suppressor, p53, enhances the post-transcriptional maturation of several miRNAs with growth-suppressive function, including miR-16-..
TP53 mutations in human cancers: origins, consequences, and clinical useMagali Olivier
Group of Molecular Carcinogenesis, International Agency for Research on Cancer, 150 cours Albert Thomas, 69372 Lyon Cedex 08, France
Cold Spring Harb Perspect Biol 2:a001008. 2010..All mutations found in human cancers are compiled in the IARC TP53 Database (http://www-p53.iarc.fr/)...
Understanding the function-structure and function-mutation relationships of p53 tumor suppressor protein by high-resolution missense mutation analysisShunsuke Kato
Department of Clinical Oncology, Institute of Development, Aging, and Cancer, Tohoku University, Sendai 980 8575, Japan
Proc Natl Acad Sci U S A 100:8424-9. 2003Inactivation of the tumor suppressor p53 by missense mutations is the most frequent genetic alteration in human cancers...
Recurrent initiation: a mechanism for triggering p53 pulses in response to DNA damageEric Batchelor
Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA
Mol Cell 30:277-89. 2008DNA damage initiates a series of p53 pulses. Although much is known about the interactions surrounding p53, little is known about which interactions contribute to p53's dynamical behavior...
Acetylation is indispensable for p53 activationYi Tang
Institute for Cancer Genetics, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA
Cell 133:612-26. 2008The activation of the tumor suppressor p53 facilitates the cellular response to genotoxic stress; however, the p53 response can only be executed if its interaction with its inhibitor Mdm2 is abolished...
Acetylation of p53 inhibits its ubiquitination by Mdm2Muyang Li
Institute for Cancer Genetics, and Department of Pathology, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA
J Biol Chem 277:50607-11. 2002In response to DNA damage, the activity of the p53 tumor suppressor is modulated by protein stabilization and post-translational modifications including acetylation...
HIF-1 antagonizes p53-mediated apoptosis through a secreted neuronal tyrosinaseAtaman Sendoel
Institute of Molecular Life Sciences, University of Zurich, Winterthurerstrasse 190, CH 8057 Zurich, Switzerland
Nature 465:577-83. 2010..germ cell apoptosis by antagonizing the function of CEP-1, the homologue of the tumour suppressor p53. The antiapoptotic property of HIF-1 is mediated by means of transcriptional upregulation of the tyrosinase family ..
Regulation of p53 activity through lysine methylationSergei Chuikov
Howard Hughes Medical Institute, Division of Nucleic Acids Enzymology, Department of Biochemistry, Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA
Nature 432:353-60. 2004b>p53 is a tumour suppressor that regulates the cellular response to genotoxic stresses. p53 is a short-lived protein and its activity is regulated mostly by stabilization via different post-translational modifications...
Gain of function of mutant p53 by coaggregation with multiple tumor suppressorsJie Xu
Switch Laboratory, Flanders Institute for Biotechnology, Vrije Universiteit Brussel, Brussels, Belgium
Nat Chem Biol 7:285-95. 2011Many p53 missense mutations possess dominant-negative activity and oncogenic gain of function...
Activated AKT regulates NF-kappaB activation, p53 inhibition and cell survival in HTLV-1-transformed cellsSoo Jin Jeong
Virus Tumor Biology Section, Laboratory of Cellular Oncology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 5055, USA
Oncogene 24:6719-28. 2005..that AKT is activated in HTLV-1-transformed cells and that Tax activation of AKT is linked to NF-kappaB activation, p53 inhibition and cell survival...
Ribosomal protein L11 negatively regulates oncoprotein MDM2 and mediates a p53-dependent ribosomal-stress checkpoint pathwayYanping Zhang
Department of Molecular and Cellular Oncology, The University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA
Mol Cell Biol 23:8902-12. 2003The gene encoding p53 mediates a major tumor suppression pathway that is frequently altered in human cancers. p53 function is kept at a low level during normal cell growth and is activated in response to various cellular stresses...
Shaping genetic alterations in human cancer: the p53 mutation paradigmThierry Soussi
Université P M Curie, 4 place Jussieu, 75005 Paris, France
Cancer Cell 12:303-12. 2007b>p53 mutations are found in 50% of human cancers. Molecular epidemiology has shown strong correlations between the spectrum of p53 mutations and exposure to exogenous carcinogens...
Ribosomal protein L23 activates p53 by inhibiting MDM2 function in response to ribosomal perturbation but not to translation inhibitionMu Shui Dai
Department of Biochemistry and Molecular Biology, Oregon Health and Science University, 3181 SW Sam Jackson Park Rd, Portland, OR 97201, USA
Mol Cell Biol 24:7654-68. 2004The p53-MDM2 feedback loop is vital for cell growth control and is subjected to multiple regulations in response to various stress signals. Here we report another regulator of this loop...
Stabilization of wild-type p53 by hypoxia-inducible factor 1alphaW G An
Department of Cell and Cancer Biology, Medicine Branch, NCI, NIH, Bethesda, Maryland 20892, USA
Nature 392:405-8. 1998Although hypoxia (lack of oxygen in body tissues) is perhaps the most physiological inducer of the wild-type p53 gene, the mechanism of this induction is unknown...
Structure of tumor suppressor p53 and its intrinsically disordered N-terminal transactivation domainMark Wells
MRC Centre for Protein Engineering, Hills Road, Cambridge CB2 0QH, United Kingdom
Proc Natl Acad Sci U S A 105:5762-7. 2008..Having solved the quaternary structure of the folded domains in the tumor suppressor p53 by a multidisciplinary approach, we have now determined the average ensemble structure of the intrinsically ..
A Mutant-p53/Smad complex opposes p63 to empower TGFbeta-induced metastasisMaddalena Adorno
Department of Histology, Microbiology and Medical Biotechnologies, University of Padua School of Medicine, viale Colombo 3, 35100 Padua, Italy
Cell 137:87-98. 2009..Here, we show that TGFbeta-dependent cell migration, invasion and metastasis are empowered by mutant-p53 and opposed by p63...
PIK3CA mutation is associated with poor prognosis among patients with curatively resected colon cancerShuji Ogino
Department of Medical Oncology, Dana Farber Cancer Institute, Brigham and Women s Hospital, Harvard Medical School, 44 Binney St, Room JF 215C, Boston, MA 02115 USA
J Clin Oncol 27:1477-84. 2009..PIK3CA mutation and subsequent activation of the AKT pathway play an important role in colorectal carcinogenesis. However, little is known about the prognostic role of PIK3CA mutation in colon cancer...
Synergistic activation of transcription by CBP and p53W Gu
Laboratory of Biochemistry and Molecular Biology, The Rockefeller University, New York 10021, USA
Nature 387:819-23. 1997The tumour suppressor p53 is a transcriptional regulator whose ability to inhibit cell growth is dependent upon its transactivation function...
Crystal structure of the tetramerization domain of the p53 tumor suppressor at 1.7 angstromsP D Jeffrey
Cellular Biochemistry and Biophysics Program, Memorial Sloan Kettering Cancer Center, New York, NY 10021
Science 267:1498-502. 1995The p53 protein is a tetrameric transcription factor that plays a central role in the prevention of neoplastic transformation...
p53 proteasomal degradation: poly-ubiquitination is not the whole storyGad Asher
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel
Cell Cycle 4:1015-8. 2005..Studies on the tumor suppressor p53 have indeed demonstrated that poly-ubiquitination of p53 by different E3 ubiquin ligases targets p53 for ..
Regulation of nucleolar signalling to p53 through NEDDylation of L11Anders Sundqvist
Wellcome Trust Centre for Gene Regulation and Expression, College of Life Sciences, University of Dundee, Dundee, Scotland, UK
EMBO Rep 10:1132-9. 2009Several studies have shown that ribosomal proteins (RPs) are important mediators of p53 activation in response to nucleolar disruption; however, the pathways that control this signalling function of RPs are currently unknown...
Phosphorylation by aurora kinase A induces Mdm2-mediated destabilization and inhibition of p53Hiroshi Katayama
Department of Molecular Pathology, Division of Pathology and Laboratory Medicine, University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA
Nat Genet 36:55-62. 2004..chromosome instability and oncogenic transformation, a phenotype characteristic of loss-of-function mutations of p53. Here we show that aurora kinase A phosphorylates p53 at Ser315, leading to its ubiquitination by Mdm2 and ..
Glutaminase 2, a novel p53 target gene regulating energy metabolism and antioxidant functionWenwei Hu
Cancer Institute of New Jersey, University of Medicine and Dentistry of New Jersey, New Brunswick, NJ 08903, USA
Proc Natl Acad Sci U S A 107:7455-60. 2010..cycle arrest, apoptosis, and senescence are traditionally thought of as the major functions of the tumor suppressor p53, recent studies revealed two unique functions for this protein: p53 regulates cellular energy metabolism and ..
p53 prevents progression of nevi to melanoma predominantly through cell cycle regulationTamara Terzian
Department of Dermatology and Charles C Gates Center for Regenerative Medicine and Stem Cell Biology, UC Denver, Aurora, CO 80045, USA
Pigment Cell Melanoma Res 23:781-94. 2010b>p53 is the central member of a critical tumor suppressor pathway in virtually all tumor types, where it is silenced mainly by missense mutations. In melanoma, p53 predominantly remains wild type, thus its role has been neglected...
Regulation of HDM2 activity by the ribosomal protein L11Marion A E Lohrum
Regulation of Cell Growth Laboratory, NCI FRCDC, Frederick, MD 21702, USA
Cancer Cell 3:577-87. 2003The HDM2 protein plays an important role in regulating the stability and function of the p53 tumor suppressor protein...
p53 regulates mitochondrial respirationSatoaki Matoba
Cardiology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA
Science 312:1650-3. 2006..Here, we show that p53, one of the most frequently mutated genes in cancers, modulates the balance between the utilization of respiratory ..
p53-Repressed miRNAs are involved with E2F in a feed-forward loop promoting proliferationRan Brosh
Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel
Mol Syst Biol 4:229. 2008..we investigated the mammalian cell proliferation control network consisting of transcriptional regulators, E2F and p53, their targets and a family of 15 miRNAs...
Nutlin-3a activates p53 to both down-regulate inhibitor of growth 2 and up-regulate mir-34a, mir-34b, and mir-34c expression, and induce senescenceKensuke Kumamoto
Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892 4258, USA
Cancer Res 68:3193-203. 2008Nutlin-3, an MDM2 inhibitor, activates p53, resulting in several types of cancer cells undergoing apoptosis. Although p53 is mutated or deleted in approximately 50% of all cancers, p53 is still functionally active in the other 50%...
Yin Yang 1 is a negative regulator of p53Guangchao Sui
Department of Pathology, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA
Cell 117:859-72. 2004..We find that YY1 ablation results in p53 accumulation due to a reduction of p53 ubiquitination in vivo...
Origin licensing and p53 status regulate Cdk2 activity during G(1)Kathleen R Nevis
Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC 27599, USA
Cell Cycle 8:1952-63. 2009..Co-depletion of Cdc6 and p53 in normal cells restored Cdk2 activation and Rb phosphorylation, permitting them to enter S phase with a reduced ..
Ribosomal protein S7 is both a regulator and a substrate of MDM2Yan Zhu
Department of Biological Sciences, Columbia University, New York, NY 10027, USA
Mol Cell 35:316-26. 2009..S7, and this interaction is required to inhibit MDM2's E3 ligase activity, leading to stabilization of MDM2 and p53. Notably, the MDM2 homolog MDMX facilitates the inhibition of MDM2 E3 ligase activity by S7...
C-terminal modifications regulate MDM2 dissociation and nuclear export of p53Stephanie Carter
The Beatson Institute for Cancer Research, Garscube Estate, Switchback Road, Glasgow G61 1BD, UK
Nat Cell Biol 9:428-35. 2007b>p53 functions to prevent malignant progression, in part by inhibiting proliferation or inducing the death of potential tumour cells...
PRIMA-1 reactivates mutant p53 by covalent binding to the core domainJeremy M R Lambert
Department of Oncology Pathology, Cancer Center Karolinska, Karolinska Institutet, SE 171 76 Stockholm, Sweden International Agency for Research on Cancer, 150 cours Albert Thomas, 69372 Lyon Cedex 08, France
Cancer Cell 15:376-88. 2009Restoration of wild-type p53 expression triggers cell death and eliminates tumors in vivo...
Inhibition of MDM2-mediated p53 ubiquitination and degradation by ribosomal protein L5Mu Shui Dai
Department of Biochemistry and Molecular Biology, School of Medicine, Oregon Health and Science University, Portland, Oregon 97201, USA
J Biol Chem 279:44475-82. 2004..Both L11 and L23 have been shown to activate p53 by inhibiting MDM2-mediated p53 suppression. Here we have shown that L5 also activates p53...
Mdm2-mediated NEDD8 conjugation of p53 inhibits its transcriptional activityDimitris P Xirodimas
University of Dundee, Ninewells Hospital and Medical School, Department of Surgery and Molecular Oncology, Dundee DD1 9SY, UK
Cell 118:83-97. 2004..Here, we show that the Mdm2 RING finger E3 ubiquitin ligase can also promote NEDD8 modification of the p53 tumor suppressor protein...
Monoubiquitylation promotes mitochondrial p53 translocationNatasha D Marchenko
Department of Pathology, Stony Brook University, Stony Brook, New York, NY 11794 869, USA
EMBO J 26:923-34. 2007A major function of the p53 tumor suppressor is the induction of a pleiotropic apoptotic program in response to stress through transcription-dependent and -independent mechanisms...
hSIR2(SIRT1) functions as an NAD-dependent p53 deacetylaseH Vaziri
Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA
Cell 107:149-59. 2001DNA damage-induced acetylation of p53 protein leads to its activation and either growth arrest or apoptosis. We show here that the protein product of the gene hSIR2(SIRT1), the human homolog of the S...
Rescue of p53 function by small-molecule RITA in cervical carcinoma by blocking E6-mediated degradationCarolyn Ying Zhao
Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden
Cancer Res 70:3372-81. 2010Proteasomal degradation of p53 by human papilloma virus (HPV) E6 oncoprotein plays a pivotal role in the survival of cervical carcinoma cells...
Inhibition of β-TrcP-dependent ubiquitination of p53 by HIV-1 Vpu promotes p53-mediated apoptosis in human T cellsSachin Verma
Laboratory of Virology, National Institute of Immunology, New Delhi, India
Blood 117:6600-7. 2011..of wild-type Vpu protein with SCF complex leads to inhibition of ubiquitination and proteasomal degradation of p53 protein in a β-TrcP-dependent manner...
Loss of HAUSP-mediated deubiquitination contributes to DNA damage-induced destabilization of Hdmx and Hdm2Erik Meulmeester
Department of Molecular and Cell Biology, Leiden University Medical Center, P O Box 9503, 2300 RA Leiden, The Netherlands
Mol Cell 18:565-76. 2005The p53 tumor suppressor protein has a major role in protecting the integrity of the genome. In unstressed cells, p53 is maintained at low levels by the ubiquitin-proteasome pathway...
The regulation of p53 by phosphorylation: a model for how distinct signals integrate into the p53 pathwayNicola J MacLaine
University of Edinburgh, Institute of Genetics and Molecular Medicine, CRUK p53 Signal Transduction Laboratories, Edinburgh, EH4 2XR, Scotland, UK
Aging (Albany NY) 1:490-502. 2009The tumour suppressor p53 is a transcription factor that has evolved the ability to integrate distinct environmental signals including DNA damage, virus infection, and cytokine signaling into a common biological outcome that maintains ..
A comparison between p53 accumulation determined by immunohistochemistry and TP53 mutations as prognostic variables in tumours from breast cancer patientsJan Alsner
Department of Experimental Clinical Oncology, Aarhus University Hospital, Aarhus, Denmark
Acta Oncol 47:600-7. 2008b>p53 accumulation and TP53 mutations are known prognostic markers for breast cancer...
Aurora-A abrogation of p53 DNA binding and transactivation activity by phosphorylation of serine 215Qiyuan Liu
Departments of Pathology and Interdisciplinary Oncology, University of South Florida College of Medicine and H Lee Moffitt Cancer Center, Tampa, Florida 33612, USA
J Biol Chem 279:52175-82. 2004The tumor suppressor p53 is important in the decision to either arrest cell cycle progression or induce apoptosis in response to a variety of stimuli...
H2AX is required for cell cycle arrest via the p53/p21 pathwayMichalis Fragkos
Ecole Polytechnique Federale de Lausanne, Faculty of Life Sciences, Swiss Institute for Experimental Cancer Research, 1015 Lausanne, Switzerland
Mol Cell Biol 29:2828-40. 2009..The results establish a new role for H2AX in the p53/p21 pathway and indicate that H2AX is required for p21-induced cell cycle arrest after replication stalling.
Estrogen receptor alpha inhibits p53-mediated transcriptional repression: implications for the regulation of apoptosisAejaz Sayeed
Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Buffalo, New York 14263, USA
Cancer Res 67:7746-55. 2007Estrogen receptor alpha (ERalpha) and tumor suppressor protein p53 exert opposing effects on cellular proliferation. As a transcriptional regulator, p53 is capable of activating or repressing various target genes...
Crystal structure of the p53 core domain bound to a full consensus site as a self-assembled tetramerYongheng Chen
Molecular and Computational Biology, Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA
Structure 18:246-56. 2010Recent studies suggest that p53 binds predominantly to consensus sites composed of two decameric half-sites with zero spacing in vivo...
Stabilization and activation of p53 downregulates mTOR signaling through AMPK in mantle cell lymphomaE Drakos
Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Leukemia 23:784-90. 2009..A high proportion of MCL tumors harbor wild-type (wt) and potentially functional p53 gene...
Direct, activating interaction between glycogen synthase kinase-3beta and p53 after DNA damagePiyajit Watcharasit
Departments of Psychiatry and Behavioral Neurobiology and Cell Biology, University of Alabama, Birmingham, AL 35294 0017, USA
Proc Natl Acad Sci U S A 99:7951-5. 2002..DNA damage induced by camptothecin, which activates the tumor suppressor p53, was found to activate GSK3beta...
The conformationally flexible S9-S10 linker region in the core domain of p53 contains a novel MDM2 binding site whose mutation increases ubiquitination of p53 in vivoHarumi Shimizu
Department of Molecular and Cellular Pathology, The Cancer Research UK Laboratories, The University of Dundee, Dundee DD1 9SY, Scotland
J Biol Chem 277:28446-58. 2002Although the N-terminal BOX-I domain of the tumor suppressor protein p53 contains the primary docking site for MDM2, previous studies demonstrated that RNA stabilizes the MDM2.p53 complex using a p53 mutant lacking the BOX-I motif...
p53 inactivation by MDM2 and MDMX negative feedback loops in testicular germ cell tumorsBaozong Li
Molecular Oncology Department, Moffitt Cancer Center, Tampa, FL, USA
Cell Cycle 9:1411-20. 2010Testicular germ cell tumors (TGCT) are unique in their excellent response to DNA-damaging chemotherapy. Mutation of p53 is rare in both untreated and relapsed TGCTs, suggesting that p53 fails to respond effectively against malignant ..
Redefining the p53 response elementBei Wang
Laboratory of Immunogenetics, Singapore Immunology Network, A STAR, 8A Biomedical Grove, Immunos, Singapore
Proc Natl Acad Sci U S A 106:14373-8. 2009The tumor suppressor p53 is a master transcriptional regulator that affects a diverse range of cellular events...
Resveratrol suppresses IGF-1 induced human colon cancer cell proliferation and elevates apoptosis via suppression of IGF-1R/Wnt and activation of p53 signaling pathwaysJairam Vanamala
Department of Food Science and Human Nutrition, 226 Gifford Building, Colorado State University, Fort Collins, CO 80523 1571, USA
BMC Cancer 10:238. 2010....
Differential sensitivity of malignant glioma cells to methylating and chloroethylating anticancer drugs: p53 determines the switch by regulating xpc, ddb2, and DNA double-strand breaksLuis F Z Batista
Department of Toxicology, University of Mainz, Mainz, Germany
Cancer Res 67:11886-95. 2007..Here we show that ACNU and BCNU induce apoptosis in U87MG [p53 wild-type (p53wt)] and U138MG [p53 mutant (p53mt)] glioma cells...
Gene expression profiling by microarray analysis reveals an important role for caspase-1 in dengue virus-induced p53-mediated apoptosisA M A Nasirudeen
Institute of Molecular and Cell Biology, Proteos, Singapore, Singapore
J Med Virol 81:1069-81. 2009Recently, a dengue virus-induced apoptosis p53- and mitochondria-mediated were reported in human and animal cells...
5-fluorouracil activation of p53 involves an MDM2-ribosomal protein interactionXiao Xin Sun
Department of Biochemistry and Molecular Biology, School of Medicine, Oregon Health and Science University, Portland, Oregon 97239, USA
J Biol Chem 282:8052-9. 2007..The anti-tumor activity of 5-FU has been attributed in part to its ability to induce p53-dependent cell growth arrest and apoptosis...
TP53 cancerous mutations exhibit selection for translation efficiencyYedael Y Waldman
Department of Molecular Microbiology and Biotechnology, Blavatnik School of Computer Science, Tel Aviv University, Ramat Aviv, Israel
Cancer Res 69:8807-13. 2009..Taken together, these results show that TE plays an important role in the selection of TP53 cancerous mutations...
Targeted rescue of a destabilized mutant of p53 by an in silico screened drugFrank M Boeckler
Centre for Protein Engineering, Medical Research Council Centre, Hills Road, Cambridge CB2 0QH, United Kingdom
Proc Natl Acad Sci U S A 105:10360-5. 2008The tumor suppressor p53 is mutationally inactivated in approximately 50% of human cancers. Approximately one-third of the mutations lower the melting temperature of the protein, leading to its rapid denaturation...
p53: 25 years after its discoveryLorne J Hofseth
Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
Trends Pharmacol Sci 25:177-81. 2004Since its discovery 25 years ago, the p53 protein has emerged as a key tumor suppressor protein at the crossroads of cellular stress response pathways...
Ribosomal protein S7 as a novel modulator of p53-MDM2 interaction: binding to MDM2, stabilization of p53 protein, and activation of p53 functionD Chen
Department of Pharmacology and Toxicology, Division of Clinical Pharmacology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
Oncogene 26:5029-37. 2007As a major negative regulator of p53, the MDM2 oncogene plays an important role in carcinogenesis and tumor progression. MDM2 promotes p53 proteasomal degradation and negatively regulates p53 function...
Germ-line transmission of a mutated p53 gene in a cancer-prone family with Li-Fraumeni syndromeS Srivastava
Department of Pathology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814 4799
Nature 348:747-9. 1990..The suppressor gene, p53, is affected in such a manner by numerous mutations, which occur in a variety of human tumours...
Modulation of the oligomerization state of p53 by differential binding of proteins of the S100 family to p53 monomers and tetramersJan van Dieck
Medical Research Council MRC Laboratory of Molecular Biology and MRC Centre for Protein Engineering, Hills Road, Cambridge CB2 0QH, United Kingdom
J Biol Chem 284:13804-11. 2009..the ways S100B, S100A1, S100A2, S100A4, and S100A6 bind to the different oligomeric forms of the tumor suppressor p53 in vitro, using analytical ultracentrifugation and multiangle light scattering...
Chromatin immunoprecipitation-on-chip reveals stress-dependent p53 occupancy in primary normal cells but not in established cell linesHelena Shaked
Department of Molecular Biology, Microarray Service Laboratory, The Core Research Facility, and Lautenberg Center for General and Tumor Immunology, Hebrew University Medical School, Jerusalem, Israel
Cancer Res 68:9671-7. 2008The p53 tumor suppressor protein is a transcription factor that plays a key role in the cellular response to stress and cancer prevention...
Electron microscopy studies on the quaternary structure of p53 reveal different binding modes for p53 tetramers in complex with DNARoberto Melero
Centro Nacional de Biotecnologia, Darwin 3, 28049 Madrid, Spain
Proc Natl Acad Sci U S A 108:557-62. 2011The multidomain homotetrameric tumor suppressor p53 has two modes of binding dsDNA that are thought to be responsible for scanning and recognizing specific response elements (REs). The C termini bind nonspecifically to dsDNA...
Synergistic decline in expressions of p73 and p21 with invasion in esophageal cancersNorihiro Masuda
First Department of Surgery and Second Department of Pathology, Gunma University School of Medicine, Maebashi 371 8551, Japan
Cancer Sci 94:612-7. 2003The significance of the p73 gene, a homologue of the p53 gene, in esophageal cancers is not fully understood...
Activating transcription factor 3 activates p53 by preventing E6-associated protein from binding to E6Hongbo Wang
Center for Cell Biology and Cancer Research, Albany Medical College, Albany, New York 12208, USA
J Biol Chem 285:13201-10. 2010..that can interact with a cellular ubiquitin ligase E6-associated protein (E6AP) and target the tumor suppressor p53 for ubiquitin-mediated proteolysis. Currently, how this critical event is regulated is largely unknown...
Cyclic pifithrin-alpha sensitizes wild type p53 tumor cells to antimicrotubule agent-induced apoptosisValentina Zuco
Department of Experimental Oncology and Laboratories, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy
Neoplasia 10:587-96. 2008As a consequence of multiple functions of p53, its activation in response to cytotoxic stress may have proapoptotic or protective effects depending on the nature of lesions...
Folding and misfolding mechanisms of the p53 DNA binding domain at physiological temperatureJames S Butler
Department of Biochemistry and Molecular Biology, SUNY Upstate Medical University, Syracuse, New York 13210, USA
Protein Sci 15:2457-65. 2006b>p53 modulates a large number of cellular response pathways and is critical for the prevention of cancer...
Mutual dependence of MDM2 and MDMX in their functional inactivation of p53Jijie Gu
Department of Cancer Cell Biology, Harvard School of Public Health, Boston, Massachusetts 02115, USA
J Biol Chem 277:19251-4. 2002MDMX, an MDM2-related protein, has emerged as yet another essential negative regulator of p53 tumor suppressor, since loss of MDMX expression results in p53-dependent embryonic lethality in mice...
p53 regulates Toll-like receptor 3 expression and function in human epithelial cell linesManabu Taura
Department of Molecular Medicine, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5 1 Oe honmachi, Kumamoto 862 0973, Japan
Mol Cell Biol 28:6557-67. 2008..Here we show that the tumor suppressor p53 positively regulates the transcription of TLR3, a receptor for viral double-stranded RNA and poly(I-C), by binding ..
Ellagic acid potentiates the effect of quercetin on p21waf1/cip1, p53, and MAP-kinases without affecting intracellular generation of reactive oxygen species in vitroSusanne U Mertens-Talcott
Department of Food Science and Human Nutrition, Institute of Food and Agricultural Sciences, University of Florida, Gainesville, FL 32611 0370, USA
J Nutr 135:609-14. 2005..We found that quercetin and combinations of quercetin and ellagic acid nonsynergistically increased p53 protein levels...
Biogenesis of p53 involves cotranslational dimerization of monomers and posttranslational dimerization of dimers. Implications on the dominant negative effectChris D Nicholls
Department of Microbiology and Infectious Diseases, Cancer Biology Research Group, University of Calgary Health Sciences Centre, Calgary, Alberta, Canada, T2N 4N1
J Biol Chem 277:12937-45. 2002Precisely how mutant p53 exerts a dominant negative effect over wild type p53 has been an enigma. To understand how wild type and mutant p53 form hetero-oligomers, we studied p53 biogenesis in vitro...
Molecular genetic analysis of p53 intratumoral heterogeneity in human astrocytic brain tumorsZhi Ping Ren
Department of Genetics and Pathology, Uppsala University, University Hospital, Uppsala, Sweden
J Neuropathol Exp Neurol 66:944-54. 2007We investigated genetic heterogeneity of astrocytic gliomas using p53 gene mutations as a marker...
MDM2-dependent downregulation of p21 and hnRNP K provides a switch between apoptosis and growth arrest induced by pharmacologically activated p53Martin Enge
Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, SE 171 77 Stockholm, Sweden
Cancer Cell 15:171-83. 2009We have previously identified the p53-reactivating compound RITA in a cell-based screen. Here, using microarray analysis, we show that the global transcriptional response of tumor cells to RITA is p53 dependent...
Guanidine alkaloid analogs as inhibitors of HIV-1 Nef interactions with p53, actin, and p56lckAllison Olszewski
Department of Chemistry, University of California, Irvine, CA 92697 2025, USA
Proc Natl Acad Sci U S A 101:14079-84. 2004..Nef from HIV(NL4-3) were used to identify a series of guanidine alkaloid-based inhibitors of Nef interactions with p53, actin, and p56(lck)...
Research Grants
- Synthetic Lethal Targeting of p53 in MyelodysplasiaA Look; Fiscal Year: 2009..targeted therapy for a subset of MDS patients defined by a high frequency of complex aberrant karyotypes and p53 mutations (MDS-CAK, ~20% of all MDS cases)...
- Synthetic Lethal Targeting of p53 in MyelodysplasiaA Look; Fiscal Year: 2007..targeted therapy for a subset of MDS patients defined by a high frequency of complex aberrant karyotypes and p53 mutations (MDS-CAK, ~20% of all MDS cases)...
- Synthetic Lethal Targeting of p53 in MyelodysplasiaA Thomas Look; Fiscal Year: 2010..targeted therapy for a subset of MDS patients defined by a high frequency of complex aberrant karyotypes and p53 mutations (MDS-CAK, ~20% of all MDS cases)...
- The role of DNA polymerase eta in DNA damage response and p53 activationXinbin Chen; Fiscal Year: 2010..PUBLIC HEALTH RELEVANCE: It is well-known that loss of p53 tumor suppressor leads to genome instability and Xeroderma Pigmentosum (XP) patients often exhibit a high frequency of ..
- CHARACTERIZATION OF NEW HUMAN P53 DISSOCIATORSRainer Brachmann; Fiscal Year: 2004The human tumor suppressor protein and transcription factor p53 integrates stress signals, such as DNA damage, hypoxia and ribonucleotide depletion, and induces either cell cycle arrest or apoptosis...
- MDMX REGULATION OF THE P53 TUMOR SUPPRESSOR PROTEINSTEVEN BERBERICH; Fiscal Year: 2004..Inactivation of the p53 tumor suppressor gene represents the most common genetic abnormality found in human cancer [1]...
- Functional Analysis of p53 Polymorphic VariantsMaureen E Murphy; Fiscal Year: 2010The central importance of the p53 tumor suppressor gene to human cancer research is best epitomized by the following facts: 1) p53 is the most frequently mutated gene in human cancer;2) p53 is a central signaling molecule in DNA damage-..
- MCAV in Organ-Confined Bladder CA based on p53 StatusRichard Cote; Fiscal Year: 2006This is a renewal application to our on-going "p53/MVAC" study. Tumor progression in transitional cell carcinoma (TCC) of the urinary bladder is believed to occur through a multistep accumulation of genetic alterations...
- DEPENDENCE OF P53 ON THIOL MAINTENANCE PROTEINSGary Merrill; Fiscal Year: 2001Stimulation of transcription by the human tumor suppressor protein p53 is compromised in yeast lacking the enzyme thioredoxin reductase (Trr1). The result suggests that p53 is prone to oxidative inactivation...
- Gene Delivery of P53 in a Tumor-bearing Mouse ModelARCHIBALD MIXSON; Fiscal Year: 2007Systemic gene delivery of p53 with cationic liposomes has been shown to reduce tumor growth in pre-clinical models...
- Skin Cancer Chemoprevention by Silibinin: Mechanisms and EfficacyRajesh Agarwal; Fiscal Year: 2010..These initiated cells harbor mutations primarily in p53 tumor suppressor gene that eventually lead to their clonal expansion and formation of skin tumors...
- Mechanisms of p53 activation in tumorsuppressionWei Gu; Fiscal Year: 2010..PUBLIC HEALTH RELEVANCE: The p53 tumor suppressor is mutated in every type of human cancers...
- Study of a FACTp140-SSRP1-associated p53 KinaseHua Lu; Fiscal Year: 2006..of this proposal is to understand the molecular and biochemical basis underlying the regulation of the p53 tumor suppressor protein in mammalian systems...
- Mechanism of p53-Mediated Tumor SuppressionXinbin Chen; Fiscal Year: 2010b>p53 tumor suppressor is a transcription factor and can be activated in response to various stress signals, including DNA damage, oncogene activation, and hypoxia...
- PROPERTIES AND REGULATION OF P53 IN TUMOR CELLSCarol Prives; Fiscal Year: 2010The p53 tumor suppressor protein is likely the most well studied mammalian transcription factor...
- Chemical Modulators for p53 Functions in Transcriptional RegulationSYED S MUJTABA; Fiscal Year: 2011DESCRIPTION (provided by applicant): The most essential human tumor suppressor protein p53 is mutated in more than 50% of the human cancers...
- p53 Acetylation and Deacetylation in TumorigenesisWei Gu; Fiscal Year: 2010The tumor suppressor gene p53 is mutated in more than 50% of human tumors...
- Chemical Modulators for p53 Functions in Transcriptional RegulationSYED S MUJTABA; Fiscal Year: 2010The most essential human tumor suppressor protein p53 is mutated in more than 50% of the human cancers...
- Polyoma Virus Disrupts ARF Signaling to p53Michael Fried; Fiscal Year: 2010..ARF can activate a p53 response resulting in cell cycle arrest or apoptotic cell death. The ARF-p53 tumor suppressor pathway is one of the cell's major defense mechanisms against cancer induced by activating oncogenes ..
- EBNA3C and tumor supressorsErle S Robertson; Fiscal Year: 2010..Thently we have shown that EBNA3C can also interact with the p53 tumor suppressor and this application will focus on developing a model to elucidate the functional significance of this ..
- Polyoma Virus Disrupts ARF Signaling to p53Michael Fried; Fiscal Year: 2007..ARF can activate a p53 response resulting in cell cycle arrest or apoptotic cell death. The ARF-p53 tumor suppressor pathway is one of the cell's major defense mechanisms against cancer induced by activating oncogenes and is ..
- P53 MODIFICATION AND NOVEL BIOLOGICAL FUNCTIONSGeorge Stark; Fiscal Year: 2002b>p53 plays a central role in determining how mammalian cells respond to stress. DNA damange, arrest of DNA or RNA sythesis, and inhibition of pyrimidine nucleotide synthesis all lead to both the accumulation and activation of p53...
