Journal ArticleDOI
Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours
Lawrence A. Donehower,Michele Harvey,Betty L. Slagle,Mark J. McArthur,Charles A. Montgomery,Janet S. Butel,Allan Bradley +6 more
TLDR
Observations indicate that a normal p53 gene is dispensable for embryonic development, that its absence predisposes the animal to neoplastic disease, and that an oncogenic mutant form of p53 is not obligatory for the genesis of many types of tumours.Abstract:
Mutations in the p53 tumour-suppressor gene are the most frequently observed genetic lesions in human cancers. To investigate the role of the p53 gene in mammalian development and tumorigenesis, a null mutation was introduced into the gene by homologous recombination in murine embryonic stem cells. Mice homozygous for the null allele appear normal but are prone to the spontaneous development of a variety of neoplasms by 6 months of age. These observations indicate that a normal p53 gene is dispensable for embryonic development, that its absence predisposes the animal to neoplastic disease, and that an oncogenic mutant form of p53 is not obligatory for the genesis of many types of tumours.read more
Citations
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Journal ArticleDOI
p53, the Cellular Gatekeeper for Growth and Division
TL;DR: The author regrets the lack of citations for many important observations mentioned in the text, but their omission is made necessary by restrictions in the preparation of review manuscripts.
Journal ArticleDOI
Cancer Cell Cycles
TL;DR: Genetic alterations affecting p16INK4a and cyclin D1, proteins that govern phosphorylation of the retinoblastoma protein and control exit from the G1 phase of the cell cycle, are so frequent in human cancers that inactivation of this pathway may well be necessary for tumor development.
Journal ArticleDOI
The retinoblastoma protein and cell cycle control
TL;DR: The main role of pRB is to act as a signal transducer connecting the cell cycle clock with the transcriptional machinery, allowing the clock to control the expression of banks of genes that mediate advance of the cell through a critical phase of its growth cycle.
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Oncogenic ras Provokes Premature Cell Senescence Associated with Accumulation of p53 and p16INK4a
TL;DR: It is shown that expression of oncogenic ras in primary human or rodent cells results in a permanent G1 arrest, and that the onset of cellular senescence does not simply reflect the accumulation of cell divisions, but can be prematurely activated in response to an onCogenic stimulus.
References
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Journal ArticleDOI
p53 mutations in human cancers
TL;DR: The p53 mutational spectrum differs among cancers of the colon, lung, esophagus, breast, liver, brain, reticuloendothelial tissues, and hemopoietic tissues as mentioned in this paper.
Journal ArticleDOI
The p53 tumour suppressor gene
TL;DR: The cell cycle is composed of a series of steps which can be negatively or postively regulated by various factors, chief among the negative regulators is the p53 protein, which can lead to cancer.
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Germ line p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms
David Malkin,Frederick P. Li,Frederick P. Li,Louise C. Strong,Joseph F. Fraumeni,Camille E. Nelson,Camille E. Nelson,David H. Kim,Jayne Kassel,Magdalena A. Gryka,Farideh Z. Bischoff,Michael A. Tainsky,Stephen H. Friend +12 more
TL;DR: Germ line p53 mutations have been detected in all five LFS families analyzed and can now be examined in additional families with LFS, and in other cancer patients and families with clinical features that might be attributed to the mutation.
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Association of human papillomavirus types 16 and 18 E6 proteins with p53.
TL;DR: This study shows that the E6 protein of HPV-16 is capable of binding to the cellular p53 protein, providing further evidence that the human papillomaviruses, the adenovirus type 5, and SV40 may effect similar cellular pathways in transformation.
Journal ArticleDOI
T Antigen Is Bound to a Host Protein in Sv40-Transformed Cells
TL;DR: It is reported here that the T antigen in a line of SV40-transformed mouse cells forms an oligomeric complex with a specific cell coded protein.