Opposing Effects of Ras on p53: Transcriptional Activation of mdm2 and Induction of p19ARF
Stefan Ries,Carola H. Biederer,Douglas Woods,Ohad Shifman,Senji Shirasawa,Takehiko Sasazuki,Martin McMahon,Moshe Oren,Frank McCormick +8 more
TLDR
It is shown that the mdm2 gene is also regulated by the Ras-driven Raf/MEK/MAP kinase pathway, in a p53-independent manner, and may play a key role in suppressing p53 during tumor development and treatment.About:Â
This article is published in Cell.The article was published on 2000-10-13 and is currently open access. It has received 383 citations till now. The article focuses on the topics: MAPK/ERK pathway & c-Raf.read more
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Proliferation, cell cycle and apoptosis in cancer
Gerard I. Evan,Karen H. Vousden +1 more
TL;DR: Deregulated cell proliferation provides a minimal 'platform' necessary to support further neoplastic progression and should be targeted withroit targeting to have potent and specific therapeutic consequences.
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The RB and p53 pathways in cancer
Charles J. Sherr,Frank McCormick +1 more
TL;DR: Interconnecting signaling pathways controlled by RB and p53 are discussed, attempting to explain their potentially universal involvement in the etiology of cancer.
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Control of apoptosis by p53.
Jordan S. Fridman,Scott W. Lowe +1 more
TL;DR: The current understanding of p53 illustrates how apoptosis can be integrated into a larger tumor suppressor network controlled by different signals, environmental factors, and cell type.
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A single nucleotide polymorphism in the MDM2 promoter attenuates the p53 tumor suppressor pathway and accelerates tumor formation in humans.
Gareth L. Bond,Wenwei Hu,Elisabeth E. Bond,Harlan Robins,Stuart G. Lutzker,Nicoleta C. Arva,Jill Bargonetti,Frank Bartel,Helge Taubert,Peter Wuerl,Kenan Onel,Linwah Yip,Shih-Jen Hwang,Louise C. Strong,Guillermina Lozano,Arnold J. Levine +15 more
TL;DR: A model is proposed whereby SNP309 serves as a rate-limiting event in carcinogenesis, and a single nucleotide polymorphism (SNP309) is found in the MDM2 promoter and is shown to increase the affinity of the transcriptional activator Sp1, resulting in higher levels ofMDM2 RNA and protein and the subsequent attenuation of the p53 pathway.
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MDM2, MDMX and p53 in oncogenesis and cancer therapy.
TL;DR: This Review highlights the progress made and pitfalls encountered as the field continues to search for MDM-targeted antitumour agents.
References
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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 Article
ras Oncogenes in Human Cancer: A Review
TL;DR: It appeared that ras gene mutations can be found in a variety of tumor types, although the incidence varies greatly and some evidence that environmental agents may be involved in the induction of the mutations.
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Lessons from Hereditary Colorectal Cancer
TL;DR: The authors are grateful to the members of their laboratories for their contributions to the reviewed studies and to F. Giardiello and S. Hamilton for photographs of colorectal lesions.
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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
TL;DR: 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.
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Mdm2 promotes the rapid degradation of p53
TL;DR: It is proposed that the Mdm2-promoted degradation of p53 provides a new mechanism to ensure effective termination of the p53 signal.