Search results for "Protein p53"
showing 10 items of 201 documents
Transcription, apoptosis and p53: catch-22
2005
The tumor suppressor p53 is a transcription factor and is activated in response to DNA damage or oncogenic transformation through modification of its interaction with regulatory proteins. The transcription factor activity of p53 is thought to mediate its primary functions of cell-cycle arrest and apoptosis through the gene expression it regulates, and evidence to support this interpretation continues to accumulate. However, reports of transcription-independent activities of p53, especially in the induction of apoptosis, persist. In particular, recent studies suggest that cytosolic p53 directly interacts with members of the BCL-2 family of apoptosis regulators, thereby triggering mitochondri…
Analysis of p53 and mdm2 proteins in malignant fibrous histiocytoma in absence of gene alteration: prognostic significance.
2000
TP53 and MDM2 genes and their protein expression were evaluated in frozen and paraffin-embedded tissue from 27 patients with malignant fibrous histiocytoma to elucidate the relationship between them, their implication in tumor progression mechanisms and their possible diagnostic-prognostic value in malignant fibrous histiocytoma. Single-strand conformation polymorphism analysis and direct sequencing of polymerase chain reaction-amplified DNA were used to establish two TP53 mutations (7.4%): a point mutation and a 63-bp duplication. Amplification of the MDM2 gene was observed in two tumors (7.4%) by means of Southern-blot analysis, one of them also carrying the TP53 point mutation. Immunohis…
Direct Activation of Bax by p53 Mediates Mitochondrial Membrane Permeabilization and Apoptosis
2004
The tumor suppressor p53 exerts its anti-neoplastic activity primarily through the induction of apoptosis. We found that cytosolic localization of endogenous wild-type or trans-activation–deficient p53 was necessary and sufficient for apoptosis. p53 directly activated the proapoptotic Bcl-2protein Bax in the absence of other proteins to permeabilize mitochondria and engage the apoptotic program. p53 also released both proapoptotic multidomain proteins and BH3-only proteins [Proapoptotic Bcl-2family proteins that share only the third Bcl-2homology domain (BH3)] that were sequestered by Bcl-xL. The transcription-independent activation of Bax by p53 occurred with similar kinetics and concentra…
Human Papilloma Virus-Dependent HMGA1 Expression Is a Relevant Step in Cervical Carcinogenesis
2008
HMGA1 is a member of a small family of architectural transcription factors involved in the coordinate assembly of multiprotein complexes referred to as enhanceosomes. In addition to their role in cell proliferation, differentiation, and development, high-mobility group proteins of the A type (HMGA) family members behave as transforming protoncogenes either in vitro or in animal models. Recent reports indicated that HMGA1 might counteract p53 pathway and provided an interesting hint on the mechanisms determining HMGA's transforming potential. HMGA1 expression is deregulated in a very large array of human tumors, including cervical cancer, but very limited information is available on the mole…
Wee1 inhibition potentiates Wip1-dependent p53-negative tumor cell death during chemotherapy
2016
AbstractInactivation of p53 found in more than half of human cancers is often associated with increased tumor resistance to anti-cancer therapy. We have previously shown that overexpression of the phosphatase Wip1 in p53-negative tumors sensitizes them to chemotherapeutic agents, while protecting normal tissues from the side effects of anti-cancer treatment. In this study, we decided to search for kinases that prevent Wip1-mediated sensitization of cancer cells, thereby interfering with efficacy of genotoxic anti-cancer drugs. To this end, we performed a flow cytometry-based screening in order to identify kinases that regulated the levels of γH2AX, which were used as readout. Another criter…
Apoptosis and cell cycle aberrations in epithelial odontogenic lesions : an evidence by the expression of p53, Bcl-2 and Bax
2017
Background Ameloblastoma (AMB), odontogenic keratocyst (OKC) and adenomatoid odontogenic tumor (AOT) are epithelial odontogenic lesions with diverse biologic profiles. Defects in regulation of apoptosis and cell cycle may be involved in the development and progression of those lesions, therefore we aimed to investigate the expression of Bcl-2, Bax and p53 to better understand the possible role of these proteins in AMBs, OKCs and AOTs. Material and Methods The studied sample consisted of 20 AMBs, 20 OKCs and 20 AOTs. Immunohistochemistry technique was performed for the antibodies p53, Bcl-2 and Bax. Immunoreactivity was observed in the epithelial component and positive cells were counted in …
Potential role of p53 protein as a novel biomarker of sperm quality, able to predict the success of ART techniques. EcoFoodFertility Project
2018
Introduction: Protein p53 is well known as “The guardian of genome”; it changes its concentration in human spermatozoa DNAin relation to the damage of the latter. It has been suggested thatthe role of the p53 ancestral gene was to ensure the integrity ofthe genomic germline and the fidelity of the evelopment process.The aim of this study is to evaluate if different concentrations of p53 protein in human spermatozoa could influence embryo quality and pregnancy rate and possibly representing a potential predictive marker of sperm quality for successful fertilization .Methods: From July 2013 to June 2017 we have examinatedretrospectively 79 couples with 2-5 years of infertility history.Males had…
Sequence-specific and DNA structure-dependent interactions of Escherichia coli MutS and human p53 with DNA
2013
Many proteins involved in DNA repair systems interact with DNA that has structure altered from the typical B-form helix. Using magnetic beads to immobilize DNAs containing various types of structures, we evaluated the in vitro binding activities of two well-characterized DNA repair proteins, Escherichia coli MutS and human p53. E. coli MutS bound to double-stranded DNAs, with higher affinity for a G/T mismatch compared to a G/A mismatch and highest affinity for larger non-B-DNA structures. E. coli MutS bound best to DNA between pH 6 and 9. Experiments discriminated between modes of p53-DNA binding, and increasing ionic strength reduced p53 binding to nonspecific double-stranded DNA, but had…
Progenitor death drives retinal dysplasia and neuronal degeneration in a mouse model of Atrip-Seckel syndrome
2020
ABSTRACT Seckel syndrome is a type of microcephalic primordial dwarfism (MPD) that is characterized by growth retardation and neurodevelopmental defects, including reports of retinopathy. Mutations in key mediators of the replication stress response, the mutually dependent partners ATR and ATRIP, are among the known causes of Seckel syndrome. However, it remains unclear how their deficiency disrupts the development and function of the central nervous system (CNS). Here, we investigated the cellular and molecular consequences of ATRIP deficiency in different cell populations of the developing murine neural retina. We discovered that conditional inactivation of Atrip in photoreceptor neurons …
Synergistic cytotoxic interactions between sodium butyrate, MG132 and camptothecin in human retinoblastoma Y79 cells.
2000
This paper studies the effects caused in human retinoblastoma Y79 cells by treatment with combinations of sodium butyrate, the inhibitor of topoisomerase I camptothecin and the inhibitor of 26S proteasome MG132. The combination of sodium butyrate and camptothecin resulted in a strong synergistic cytotoxicity, as revealed by combination indices of 0.77 and 0.52 calculated at IC(50) and IC(75). Synergistic interactions were also demonstrated for combinations of sodium butyrate and MG132, camptothecin and MG132 and for a combination of all three compounds. The cytotoxic effects observed after the combined treatments can be considered a consequence of apoptosis, as suggested by the appearance o…