A Comparison Of The Biological Activities Of Wild‐type And Mutant P53

Below is result for A Comparison Of The Biological Activities Of Wild‐type And Mutant P53 in PDF format. You can download or read online all document for free, but please respect copyrighted ebooks. This site does not host PDF files, all document are the property of their respective owners.

p53: oncogene or anti-oncogene?

was that the wild-type p53 is unable to complement ras, but that the mutant could do so. Examination of the se- quence and biological activity of a number of natural and synthetic mutants of p53 has confirmed and ex- tended this conclusion. Many different point, deletion,


accumulation of p53 protein, but activation of a G1-phase checkpoint by low-oxygen conditions is independent of p53 status. Mol. Cell Biol. 14, 6264-6277, 1994 1. Nakano H., Kurihara K., Okamoto M., Tone S. und Shinohara K. Heat-induced apoptosis and p53 in cultured mammalian cells. Int. J. Radiat. Biol. 71, 519-529, 1997 1.

Gain-of-Function Mutant p53 R273H Interacts with Replicating

Nov 27, 2019 Staining of p53 and PARP1 in breast cancer TMAs and comparison with the TCGA database indicated a higher double-positive signal in basal-like breast cancer than in Luminal A or Luminal B subtypes. Higher PARP1 protein levels and poly-ADP-ribosylated proteins were detected in mtp53 R273H than in wild-type p53-expressing patient-derived xenograft

A comparison of the biological activities of wild‐type and

A comparison of the biological activities of wild-type and mutant p53 GERARD P. ZAMBET I AND ARNOLD J. LEVINE Department of Moleculai Biolog Princeton University, Princeton, Ne w Jersey 08544, USA ABSTRACT Tumorigenesis is characterized by a series of genetic alterations in both dominant oncogenes and tumor suppressor genes. A hallmark of tumor

Phosphorylation at Ser-15 and Ser-392 in Mutant p53 Molecules

wild-type p53. No change was observed at Ser-9. [His273]p53, a third mutant, had a phosphorylation state similar to that of wild-type p53. We suggest that phosphorylation of Ser-15 may depend on the ability of p53 to adopt a wild-type conformation and may contribute to p53's ability to block cell growth. The most common genetic change

TNFAIP8: Inflammation, Immunity and Human Diseases

v2 induces p53-independent inhibition of DNA synthesis, widespread p53 binding, the initiation of p53-dependent cell-cycle arrest, and sensitization of cells to DNA damaging reagents [33]. Mutant p53 (p53-K120) binds with the TNFAIP8 locus at a cryptic p53 response element that is not occupied or bound by wild-type p53 and thus

Molecular mechanism and potential target indication of TAK

tive activities in RAS-mutant versus RAS wild-type cells; this finding was confirmed in pancreatic patient-derived xenografts. Comparison analysis of cell panel data also demonstrated a unique efficacy spectrum for TAK-931 compared with currently used chemotherapeutic drugs. Our findings help to elucidate the molecular mechanisms

Document4 - Cell Journal

29. Zambetti GP. Levine AJ. A comparison of the biological activities of wild-type and mutant p53. FASEB J 1993; 7:855-865 human p53 for gene therapy of cancer. Hum Gene Ther 1994; 5: 1079-1088 11. Buttgereit P, Schakowski F, Marten A, Brand K, Renoth S. Effects of adenoviral wild-type p53 gene transfer in p53-mutated lymphoma cells. Cancer Gene

Phosphorylation Ser-15 andSer-392 in mutant molecules to

also constitutively expresses a p53 mutant, [Ile237]p53. GM15.41 and GM37.0 are stable derivatives ofT98Gthat express [Ala15]p53 and [Ala37]pS3, respectively (28).

Modeling Familial Cancer with Induced Pluripotent Stem Cells

Apr 09, 2015 gene encoding the tumor suppressor p53 are responsible for LFS (Malkin et al., 1990). Mutations in p53 usually not only abolish normal p53 function but are also associated with addi-tional oncogenic activities. Despite the prevalence of p53 muta-tions, the simultaneous presence of alterations in other tumor

Wil.d-ty.pe p53 mediates apoptosis by E1A, which 1s inhibited

mutant p53 was sufficient to block apoptosis by E1A and permit transformation with high frequency. When p53 was returned to the wild-type conformation, E1A+p53 transformants underwent apoptosis. Expression of the E1B 19K protein completely prevented induction of ap- optosis by wild-type p53.

Computational Study of Transcriptional Regulation - From

activities and binding sites. Finally, we extend the DREM framework which was previously developed by our group to study dynamic regulatory networks, and we use the improved version to analyze a biological dataset of gene responses in ara-bidopsis following ethylene treatment. Together, the methods and analyses presented

BIOINFORMATICS Vol. 23 ISMB/ECCB 2007, pages i104 i114 doi:10

ments of mutant residues relative to wild-type. 4D features came from the time course of protein unfolding in a simulated heat bath, plus other computational estimates of protein thermostability. Active Learning of informative p53 cancer rescue mutants i105

p53-R273H Sustains ROS, Pro-Inflammatory Cytokine Release and

Feb 24, 2021 Abstract: p53 is the most frequently mutated or inactivated gene in cancer, as its activity is not reconcilable with tumor onset and progression. Moreover, mutations in the p53 gene give rise to mutant proteins such as p53-R273H that, besides losing the wild type p53 (wtp53) capacity to

Altered p53 functionality in cancer-associated fibroblasts

TP53 gene, resulting in production of mutant p53 proteins, can lead not only to loss of its tumor-suppressive functions but often also to gain of tumor-promoting activities, associated with al-tered p53-dependent transcriptional programs (6). Of note, al-terations in the regulatory networks that impinge on p53 may

Immunohistochemical Detection of p53 Tumor-Suppressor Protein

altered p53 protein that binds to and inactivates the normal, wild-type p53 protein (WT p53), thereby pro-moting tumorigenesis. Mutant p53 protein is more sta-ble and has an extended half-life in comparison with WT p53.14,21 These characteristics of the alteredprotein cause the protein to accumulate in the nucleus of af-

and (3) the oxidative degradation of mitochondrial components

physiological and biological properties. Expression of p53 induces human cell lines together with wild-type (WT) or mutant p53. As encode proteins with activities related to the redox

Wild-Type, but not Mutant, Human p53 Proteins Inhibit the

ties of immunoaffinity-purified wild-type or mutant human p53 or, for comparison, murine p53, were added to replica-tion reactions, and the reaction products were analyzed by Dpn I digestion of linearized 32P-labeled DNA isolated from reaction mixtures (Fig. 1A) or by acid precipitation (Fig. 1B). Both the murine and wild-type human p53

Contribution of autophagic cell death to p53-dependent cell

p53, MDM2, p21WAF1, BAX, 14-3-3sigma, DRAM and Sesn2 were analyzed by western blotting. b-Actin was used as an internal control. Numbers indicated under the top panel are the expression levels of p53⁄b-actin (expression level of wild-type [WT] p53⁄expression level of b-actin = 1.00). Numbers indicated under the other panels are the

p53 expression in human small intestinal tumors

10. Zanbetti GP and Levin AJ: A comparison of th biological activities of wild-type and mutant p53. FASEB J 7: 855-865, 1993. 11. Harris CC: Mutant p53 - The commonest genetic abnormality in human cancer? J Pathol 162: 5-6, 1990. 12. Nigro JM, Baker SJ, Preisinger AC, Jessup JM, Hostetter R,


These data led to the hypothesis that wild-type p53 transactivates a gene or set of genes involved in growth sup- pression, while mutant p53 cannot activate this pathway. Wild-type but not mutant p53 has also been shown to bind specific DNA sequences (Kern et al., 1991; Funk et al., 1992;

Gain-of-Function Mutant p53 R273H Interacts with Replicating

mutant p53 (mtp53) and some contain oncogenic gain-of-function (GOF) p53. We previously reported that GOF mtp53 R273H upregulates the chromatin association of mini chromosome maintenance (MCM)proteinsMCM2-7 and PARPandnamedthis the mtp53 PARP MCM axis. In this study, we dissected the func-tion and association between mtp53 and PARP using a

articles p53 mutant mice that display early ageing-associated

Mutant (p53+/m) mice exhibit enhanced resistance to spontaneous tumours compared with wild-type (p53 +/+ ) littermates. As p53 +/m mice age, they display an early onset of phenotypes associated

Cancer Cell Article

Comparison of the biological activities of the compounds in p53-activation assays showed that BMH-21a1 was inactive in this regard (Figure 2D). This led us to hypothesize that BMH-21 activity is conveyed by its interaction with the DNA backbone in GC-rich DNA sequences. We then sought to identify genomic DNA (1) that is GC rich,(2)

Transactivation-deficient Î TA-p73 Inhibits p53 by Direct

p73) and wild-type p53 is a sequence-specific DNA binding factor. Due to the lack of the N-terminal transactivation do-main, however, TA-p73 does not transactivate typical p53-regulated genes, resulting in an inability to induce growth arrest and apoptosis. Moreover, TA-p73 acts as a dominant-negative inhibitor of p53 and full-length p73 (TA-p73).

Keeping p53 in check: essential and synergistic functions of

p53 biological activities are the proapoptotic genes bax, PUMA and NOXA2 and the cell cycle regulators p213 and Ptprv.4 In the absence of stress signals, the p53 protein is kept in check to allow normal cell proliferation and/or maintenance of cell viability. Of critical importance for this process are the two

KREX Protein Arrays - Sengenics

1. Cy5-anti-p53 Antibody Assay 2. Cy3-GADD45 DNA Assay The p53 Protein Function Array contains 1 wild-type human p53 protein, 45 mutant p53 proteins and 8 Cy3-labelled BSA marker printed in duplicate. A scanned image of the slide ran on Assay 1 above shows a visualisation only p53 probes (Figure 6a). A scanned image of

Research Paper BMAL1 knockdown triggers different colon

on P53 activation. mTOR signaling is an evolutionarily conserved nutrient sensing pathway and a central regulator of mammalian metabolism. It has been hypothesized that increased mTOR activity could direct cell fate towards quiescence, cell death or senescence under varying P53 activation and P21 expression status [23 26].

p53 Mutations in Human Cancers

result in a mutantprotein able to bindto hsc70 (3, 29, 30). Ninety-eight percent ofthe 280 base substitution mutations in this review fall within a 600-base pair region of the p53 gene


30. Zambetti Gp, Levine AJ: A comparison of the biological activities of wild-type and mutant p53. FASEB] 7:855-865,1993 31. Vousden K: Interactions of human papilloma virus cransfonning proteins with the products of tumor suppressor genes. FASEB] 7:872-879, 1993 32. Campbell C, Quinn AG, Angus B, Rees JL: The relation between p53 mutation

Table of Contents - DTIC

REPORT DOCUMENTATION PAGE Form Approved OMB No. 0704-0188 Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the

Modulation of p53 Transactivation Domain Conformations by

suppressor p53. Through extensive sampling, in excess of 1.0 µs per replica, well-converged structural ensembles of wild-type and mutant p53-TAD as well as WT p53-TAD in the presence of EGCG were generated. The results reveal that mutants could induce local structural changes and affect secondary structural properties.

Mutant p53 gain of function is interwoven into the hallmarks

Mutant p53 GOF is interwoven into the hallmarks of cancer 477 cancer gene signature by cooperating with NFκB, com-pared with the wild-type p53 silencing or the p53 conformational mutants (Solomon H et al, unpublished data). Since it is well established that wild-type p53 and NFκB antagonize each other [37], it is not sur-

Studies of mutant p53-targeting small molecules

actually was inhibiting the normal activities of p53. It was shown that wild type p53 does not transform cells 6 and that the p53 protein can effectively inhibit oncogenic transformation of cells in culture 7. Collectively these results showed that wild type p53 really functions a potent tumor suppressor. Subsequent genetic analysis of the p53 gene

Dissection of the sequence-specific DNA binding and

The enzymatic activities of mutant p53 proteins were compared to that of wild-type p53 measured by this assay (Table 1). Exonuclease activities of H168N, H179N and H297N p53 proteins were approximately comparable to that of wild-type p53, while H193N, H214N and H233N mutant p53 proteins actually showed significantly increased

Cyclo-oxygenase2: a pharmacological target for the prevention

COX 2.16 19,42 Moreover, wild-type but not mutant P53 suppressesCOX 2transcription, raising the possibility that P53 status is also a determinant of COX 2 expression.43 In support of this notion, higher amounts of COX 2 were found in gastric cancers containing mutant P53 than in those containing wild-type P53.44

Perspective p53Designer Genes for the Modern Mouse

test p53 rescue drugs, the first goal was to show that we could retain p53 wild-type functions in the knock-in strain; the humanized mouse, when unchallenged, ideally should be indistinguishable from its wild-type counterpart, and the foreign p53 molecule should display p53 wild-type activities in mouse cells. To be broadly useful as an

Switching on p53: an essential role for protein phosphorylation?

p53 function (as well as the ability to act as a dominant negative inhibitor of wild type p53), many mutant p53 proteins acquire new activities, termed gain of function , through which they are able to directly enhance cancer progression and development. These mechanisms include interaction with p63 and p73 to inhibit their transcription

ResearchGene expression profiling of mouse p53-deficient

force inactivates the remaining wild-type allele. The majority of TP53 mutations are missense (73.6%), and many of these missense mutant p53 forms not only lose their tumor suppressive function and acquire dominant-negative activities, but also gain new oncogenic proper-ties that are independent of wild-type p53, the so called