p53: oncogene or anti-oncogene?
Genes & DevelopmentPublished 1 January 1990Open access
David P. Lane, Samuel Benchimol
Citations810
SJR quartileQ1
SJR score4.00
SNIP1.43
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MedicineBiochemistry, Genetics and Molecular Biology
ScienceThe Human Papilloma Virus-16 E7 Oncoprotein Is Able to Bind to the Retinoblastoma Gene Product
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NatureMutations in the p53 gene occur in diverse human tumour types
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ScienceChromosome 17 Deletions and p53 Gene Mutations in Colorectal Carcinomas
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The data suggest that p53 gene mutations may be involved in colorectal neoplasia, perhaps through inactivation of a tumor suppressor function of the wild-type p53 genes.
CellThe p53 proto-oncogene can act as a suppressor of transformation
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DNA clones of the wild-type p53 proto-oncogene inhibit the ability of E1Aplus ras or mutant p53 plus ras-activated oncogenes to transform primary rat embryo fibroblasts, suggesting that the p53 prototype can act negatively to block transformation.
CellCharacterization of a 54K Dalton cellular SV40 tumor antigen present in SV40-transformed cells and uninfected embryonal carcinoma cells
1,838 Citations1979Daniel I. H. Linzer, Arnold J. Levine
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CellSV40 large tumor antigen forms a specific complex with the product of the retinoblastoma susceptibility gene
1,486 Citations1988James A. DeCaprio, John W. Ludlow +7 more
Results are consistent with a model for transformation by SV40 which, at least in part, involves T/p110-114 complex formation and the perturbation of Rb protein and/or T function.
NatureAssociation between an oncogene and an anti-oncogene: the adenovirus E1A proteins bind to the retinoblastoma gene product
1,434 Citations1988Peter Whyte, Karen Buchkovich +5 more
The interaction between E1A and the retinoblastoma gene product is the first demonstration of a physical link between an oncogene and an anti-oncogene.
Sciencep53: A Frequent Target for Genetic Abnormalities in Lung Cancer
1,230 Citations1989Takashi Takahashi, Marion M. Nau +8 more
These findings, coupled with the previous demonstration of 17p allele loss in lung cancer, strongly implicate p53 as an anti-oncogene whose disruption is involved in the pathogenesis of human lung cancer.
NatureFunctional inactivation of genes by dominant negative mutations
1,179 Citations1987Ira Herskowitz
A new approach to this problem involves the manipulation of the cloned gene to create what are known as 'dominant negative' mutations, encode mutant polypeptides that when overexpressed disrupt the activity of the wild-type gene.
Molecular and Cellular BiologyActivating mutations for transformation by p53 produce a gene product that forms an hsc70-p53 complex with an altered half-life.
1,136 Citations1988Cathy A. Finlay, Philip W. Hinds +4 more
ScienceAbnormalities in Structure and Expression of the Human Retinoblastoma Gene in SCLC
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CellAdenovirus E1b-58kd tumor antigen and SV40 large tumor antigen are physically associated with the same 54 kd cellular protein in transformed cells
867 Citations1982Peter Sarnow, Ye-Shih Ho +2 more
The fact that the adenovirus and Sv40 tumor antigens, both required for transformation, can be found in physical association with the same cellular protein in a transformed cell is a good indication that these two diverse viral proteins share some common mechanisms or functions.
ScienceSuppression of the Neoplastic Phenotype by Replacement of the RB Gene in Human Cancer Cells
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NatureCooperation between gene encoding p53 tumour antigen and ras in cellular transformation
756 Citations1984Luis F. Parada, Hartmut Land +3 more
The results indicate that the p53-encoding gene can play a causal role in the conversion of normal fibroblasts into tumorigenic cells, suggesting an important role of p53 in tumorigenesis.
NatureParticipation of p53 cellular tumour antigen in transformation of normal embryonic cells
741 Citations1984Daniel Eliyahu, Avraham Raz +3 more
It is demonstrated here that p53 can cooperate with the activated Ha-ras oncogene to transform normal embryonic cells, and the resultant foci contain cells of a markedly altered morphology which produce high levels of p53.
NatureThe retinoblastoma susceptibility gene encodes a nuclear phosphoprotein associated with DNA binding activity
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Biochemical fractionation and immunofluorescence studies demonstrate that the majority of the RB protein is located within the nucleus, suggesting that the RB gene product may function in regulating other genes within the cell.
International Journal of CancerP53 expression in breast cancer
608 Citations1988Giorgio Cattoretti, Franco Rilke +3 more
It is concluded that p53 in mammary carcinomas is associated with ER‐negative, growth factor receptor‐positive, high‐grade tumors, and is a promising new parameter to evaluate the cellular biology and prognosis of breast cancer.
Journal of VirologyMutation is required to activate the p53 gene for cooperation with the ras oncogene and transformation
593 Citations1989Philip W. Hinds, Cathy A. Finlay +1 more
Quantitative improvements of transformation frequencies are associated with the higher expression levels of altered p53 protein that are provided by having one of the p53 introns in the transforming plasmid.
NatureCellular immortalization by a cDNA clone encoding the transformation-associated phosphoprotein p53
578 Citations1984John R. Jenkins, K. Rudge +1 more
Cloned complementary DNA sequences encoding murine p5318 are cloned and reported here that transfection of p53 expression constructs into cells of finite lifespan in vitro results in cellular immortality and susceptibility to transformation by a ras oncogene.
Proceedings of the National Academy of SciencesRearrangement of the p53 gene in human osteogenic sarcomas.
491 Citations1987Hatisaburo Masuda, Catherine Miller +3 more
A survey of 134 human carcinomas, sarcomas, leukemias, and lymphomas obtained at surgery or from peripheral blood found rearrangements of the p53 gene only in osteogenic sarcoms, indicating that the genetic abnormality in the tumor was acquired.
Proceedings of the National Academy of SciencesLoss of heterozygosity on chromosomes 3, 13, and 17 in small-cell carcinoma and on chromosome 3 in adenocarcinoma of the lung.
489 Citations1987Jun Yokota, M Wada +3 more
Results indicate that recessive genetic changes involving sequences on chromosomes 3p, 13q, and 17p may play important roles in the genesis of small-cell carcinoma, and those on chromosome 3P may play an important role in the Genesis of adenocarcinoma.
Proceedings of the National Academy of SciencesMajor deletions in the gene encoding the p53 tumor antigen cause lack of p53 expression in HL-60 cells.
414 Citations1985D. Wolf, Varda Rotter
It is suggested that the deficiency of the p53 protein in HL-60 cells could have been overcome by using an alternative metabolic pathway, and the c-myc product is a candidate for such an alternative protein.
NatureRearrangements of the cellular p53 gene in erythroleukaemic cells transformed by Friend virus
332 Citations1985Michael Mowat, Ambrose Cheng +3 more
It is demonstrated that genomic rearrangements are responsible for p53 gene Jnactivation in these cell lines and that they occur in vivo during the natural progression of Friend virus-induced erythroleukaemia.
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294 Citations1989HG Ahuja, Menashe Bar‐Eli +3 more
Heterogeneous alterations in the structure and expression of the p53 gene appear to be relatively frequent in blast crisis and may be involved in the evolution of disease.
Naturep53 and DNA polymerase α compete for binding to SV40 T antigen
293 Citations1987Julian Gannon, David P. Lane
It is established that p53 and DNA polymerase α can compete for binding to the SV40 T antigen and important implications for the control by these nuclear oncogenes of viral and cellular DNA synthesis and viral host range are presented.
Proceedings of the National Academy of SciencesMitotic recombination of chromosome 17 in astrocytomas.
286 Citations1989C. David James, E Carlbom +3 more
The data suggest that the somatic attainment of homozygosity for loci on chromosome 17p is frequently associated with the oncogenesis of central nervous system tumors, particularly those showing solely astrocytic differentiation, and that mitotic recombination mapping is a useful approach towards the subregional localization of a locus whose rearrangement is involved in this disease.
Journal of VirologyMonoclonal antibody analysis of p53 expression in normal and transformed cells
282 Citations1986Jonathan W. Yewdell, Julian Gannon +1 more
Using the panel of anti-p53 antibodies and sensitive immunocytochemical methods, it is found that p53 has a predominantly nuclear location in established but not transformed cells as well as in the vast majority of transformed cell lines.
CellReconstitution of p53 expression in a nonproducer Ab-MuLV-transformed cell line by transfection of a functional p53 gene
265 Citations1984D. Wolf, Nicholas Harris +1 more
The expression of p53 is essential for tumor cells to exhibit a fully transformed phenotype, manifested in lethal tumors in syngeneic mice, and is suggested to be essential for other Ab-MuLV-transformed p53-producer cell lines.
PubMedAltered expression of the retinoblastoma (RB) gene in small-cell carcinoma of the lung.
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The LancetALLELE LOSS ON SHORT ARM OF CHROMOSOME 17 IN BREAST CANCERS
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PubMedMeth A fibrosarcoma cells express two transforming mutant p53 species.
235 Citations1988Daniel Eliyahu, Naomi Goldfinger +6 more
The data indicate that these cells, derived from a chemically-induced tumor, carry two independently mutated p53 alleles, each encoding a transformationally activated protein, which may imply that the mutations in the p53 gene played a role in the development of the Meth A tumor.
NatureMouse p53 inhibits SV40 origin-dependent DNA replication
221 Citations1987Antony W. Braithwaite, Horst-Werner Sturzbecher +4 more
The data presented suggest that p53 may affect directly the initiation or maintenance of replicative DNA synthesis in mammalian cell cycle control and specifically with events occurring at the G0–G1 boundary.
Molecular and Cellular BiologyRole of the p53 protein in cell proliferation as studied by microinjection of monoclonal antibodies.
216 Citations1984W E Mercer, Carlo Avignolo +1 more
CellThe murine p53 protein blocks replication of SV40 DNA in vitro by inhibiting the initiation functions of SV40 large T antigen
215 Citations1989Edith H. Wang, Paula N. Friedman +1 more
NatureOverproduction of p53 antigen makes established cells highly tumorigenic
203 Citations1985Daniel Eliyahu, Dan Michalovitz +1 more
It is demonstrated here that overproduction of p53 in an established cell line, while not causing gross morphological changes, endows these cells with an overt tumorigenic potential, and the tumorigenics efficiency of such cell lines may be correlated with the extent of p 53 overproduction.
NatureThe cellular oncogene p53 can be activated by mutagenesis
178 Citations1985John R. Jenkins, K. Rudge +2 more
It is reported that cellular immortalization by a wild-type p53 cDNA gene is conditional upon the promoter/enhancer construction used, but that p53 can extend cellular lifespan by a second distinct mechanism involving rearrangements of the coding sequence which give rise to stable protein products.
The Journal of PathologyExpression of the nuclear oncogene p53 in colon tumours
173 Citations1989Frank M. van den Berg, A. J. Tigges +4 more
Using a monoclonal antibody to p53 antigen, immunohistochemical analysis of carcinomas and Dysplastic tubular adenomas of the colon has been performed to study the relation between p53 expression and dysplasia or malignancy.
PubMedMutant p53 proteins bind hsp 72/73 cellular heat shock-related proteins in SV40-transformed monkey cells.
163 Citations1987Stürzbecher Hw, Peter M. Chumakov +2 more
Examination of the expression of a series of mouse mutant, as well as wild-type, p53 proteins in SV40-transformed monkey COS cells shows that these proteins are identical to the hsp 72/73 heat shock proteins.
PubMedImmortalization of rat embryo fibroblasts by the cellular p53 oncogene.
156 Citations1988Benjamin Rovinski, Samuel Benchimol
It is demonstrated that elevated expression of the mouse p53 gene, driven by its natural promoter and in the absence of strong heterologous promoters and/or enhancers, can efficiently immortalize early-passage rat embryo fibroblasts.
PubMedCloning and characterization of a cDNA from Xenopus laevis coding for a protein homologous to human and murine p53.
155 Citations1987Thierry Soussi, Claude Caron de Fromentel +3 more
The in vitro transcription-translation products of the X. laevis clone were successfully immunoprecipitated by human anti-p53 sera, demonstrating that there is at least one epitope in common between theX.
NatureSimian virus 40 replication in adenovirus-transformed human cells antagonizes gene expression
145 Citations1985Jane Lebkowski, Suzanne Clancy +1 more
It is found that SV40-based vectors transfected into most human cells replicate poorly, if at all, and replication and gene expression seem to be antagonistic on the authors' vectors.
PubMedInactivation of the p53 oncogene by internal deletion or retroviral integration in erythroleukemic cell lines induced by Friend leukemia virus.
130 Citations1988Ben David Y, Prideaux Vr +3 more
Molecularly characterized the rearrangements in two murine erythroleukemic cell lines induced by Friend leukemia virus that contain a rearranged p53 gene and fail to express p53 protein and the significance of these findings with regard to the multi-stage nature of Friend virus induced erystroleukemia is discussed.
PubMedThe cellular protein p53 in human tumours.
105 Citations1984L.V. Crawford, D. Pim +1 more
Tumour tissue from patients with colorectal and mammary tumours has been assayed for the cellular protein p53 using a specific radioimmune assay and no alteration was observed which could be correlated with the increased levels of p53 in the positive tumours.
Molecular and Cellular BiologyPurification of complexes of nuclear oncogene p53 with rat and Escherichia coli heat shock proteins: in vitro dissociation of hsc70 and dnaK from murine p53 by ATP.
105 Citations1988Catherine F. Clarke, Keith C. Cheng +4 more
Molecular and Cellular BiologyDeletion of 5'-coding sequences of the cellular p53 gene in mouse erythroleukemia: a novel mechanism of oncogene regulation.
96 Citations1987Benjamin Rovinski, Donald G. Munroe +4 more
PubMedInhibition of cell growth mediated by plasmids encoding p53 anti-sense.
96 Citations1987O Shohat, Matthew Greenberg +3 more
Findings support the notion that p53 is essential for continuous cell proliferation by employing anti-sense RNA methodology to inhibit p53 expression.
Proceedings of the National Academy of SciencesIncreased expression of p53 protein in human leukemia cells.
91 Citations1986H P Koeffler, Catherine Miller +3 more
The results using fresh leukemia cells suggest that p53 may contribute to the phenotype of certain leukemias in vivo, and p53 mRNA and protein expression in a variety of human myeloid leukemia lines blocked at different stages of differentiation.
The Journal of Experimental Medicinep53 in chronic myelogenous leukemia. Study of mechanisms of differential expression.
85 Citations1988Michael Lübbert, Carl W. Miller +2 more
The study of the expression of p53 using chronic myelogenous leukemia cell lines, somatic hybrids of these cells, and leukemic cells from CML patients suggests that expression of the gene is not regulated normally in CML.
Molecular and Cellular BiologyTumorigenicity of fibroblast lines expressing the adenovirus E1a, cellular p53, or normal c-myc genes.
84 Citations1986Ameeta Kelekar, Michael D. Cole
Cancer Genetics and CytogeneticsAbnormalities of chromosome No. 17 in myeloproliferative disorders
84 Citations1982G.H. Borgström, P Vuopio +1 more
It is suggested that loss of 17p is a highly nonrandom event related to blastic crisis in CML and the terminal phase in other myeloid leukemias.
PubMedLoss of a highly conserved domain on p53 as a result of gene deletion during Friend virus-induced erythroleukemia.
72 Citations1988Munroe Dg, Benjamin Rovinski +2 more
Comparison with p53 protein from other species indicated that the region of the molecule missing in p46 included a highly conserved region, and it seems likely, therefore, that an important functional property of p53 may be affected by the mutation.
Molecular and Cellular BiologyCharacterization of mutant p53-hsp72/73 protein-protein complexes by transient expression in monkey COS cells.
71 Citations1988H W Stürzbecher, Christine M. Addison +1 more
Journal of VirologyMultistage Friend erythroleukemia: independent origin of tumor clones with normal or rearranged p53 cellular oncogenes
69 Citations1987Vincent Chow, Yaacov Ben‐David +3 more
The results suggest that Friend tumor cells with rearrangements in their p53 gene arise as the result of a unique transformation event, rather than by progression from already existing tumor cellsWith a normal p53 genes, and suggest that such rearranges confer a strong selective advantage to these cells in vivo.
NatureRepression of simian virus 40 early transcription by viral DNA replication in human 293 cells
65 Citations1985E D Lewis, James L. Manley
It is shown that the SV40 early region is expressed at an extremely low level following its introduction ito human 293 cells, contrasting with results observed in a large number of other cell lines.
PubMedMouse p53 blocks SV40 DNA replication in vitro and downregulates T antigen DNA helicase activity.
63 Citations1988Stürzbecher Hw, Ruth Brain +4 more
Althoughmouse p53 has no significant effect on T antigen encoded activities such as ATPase and DNA binding, helicase activity is somewhat reduced suggesting that the in vivo suppression by mouse p53 of SV40 replication may be due, at least in part, to direct modulation of T antigen function.
Molecular and Cellular BiologyAbelson murine leukemia virus-transformed cells that lack p53 protein synthesis express aberrant p53 mRNA species.
61 Citations1984D. Wolf, Smadar Admon +2 more
The Journal of Experimental MedicineExpression of the p53 oncogene in acute myeloblastic leukemia.
52 Citations1986Lachlan J. Smith, E. A. McCulloch +1 more
A highly significant correlation between p53 protein synthesis in leukemic blast cells and the secondary plating efficiency of these cells is found, which provides an estimate for the self renewal capacity of progenitor cells in the blast population.
Molecular and Cellular BiologyOverproduction of protein p53 contributes to simian virus 40-mediated transformation.
45 Citations1986Dan Michalovitz, Daniel Eliyahu +1 more
VirologyThe cellular tumour antigen p53: Evidence for transformation-related, immunological variants of p53
33 Citations1986Jo Milner, A Cook
The results indicate the existence of two immunologically distinct variants of p53 expressed in transformed cells that are distinguished by the presence or absence of the epitope recognised by PAb246.
Journal of VirologyThe p53 complex from monkey cells modulates the biochemical activities of simian virus 40 large T antigen
26 Citations1989L C Tack, James H. Wright +2 more
The findings imply that complex formation between cellular monkey p53 and SV40 T antigen modulates a number of essential activities of T in SV40 productive infection.
PubMedOverexpression of normal human p53 in established fibroblasts leads to their tumorigenic conversion.
25 Citations1989Savilla Tuck, L. Crawford
Data show that overproduction of normal human p53 can confer an enhanced tumorigenic phenotype on established fibroblasts and support the idea that mutational activation may be necessary for p53 to express its full oncogenic potential.
JNCI Journal of the National Cancer InstituteElevated Levels of p53 Antigen in Cultured Skin Fibroblasts From Patients With Hereditary Adenocarcinoma of the Colon and Rectum and Its Relevance to Oncogenic Mechanisms<xref ref-type="fn" rid="FN2">2</xref>
23 Citations1986Levy Kopelovich, Albert B. DeLeo
Skin fibroblasts from patients with adenomatosis of the colon and rectum (ACR) were shown, in general, to express elevated amounts of the p53 antigen as determined by immunoprecipitation with the monoclonal antibody PAb421, and results suggest that over-expression of the P53 antigen is due, in part, to the increased stability of thep53 antigen in ACR cells.
Proceedings of the National Academy of SciencesPre-crisis mouse cells show strain-specific covariation in the amount of 54-kilodalton phosphoprotein and in susceptibility to transformation by simian virus 40.
18 Citations1983S Chen, George Blanck +1 more
Mouse strains whose cells produced a high level of endogenous 54-kDa phosphoprotein on passage did not further increase its expression after simian virus 40 transformation, and in the absence of any transforming agent, the amount of endogenous 53-kilodalton phosphop protein in early pre-crisis mouse cells varied in a strain-specific way.
Cancer InvestigationSkin Fibroblasts from Humans Genetically Predisposed to Colon Cancer are Abnormally Sensitive to SV40
13 Citations1984Levy Kopelovich
Results provide additional support for the use of SV40 to identify humans at risk from ACR families as well as other dominantly transmitted forms of human cancer.