Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have shown previously that nasal natural killer (NK)/T-cell lymphoma was associated with Epstein-Barr virus (EBV) and had peculiar clinical features. However, little is known about its biological and genetic changes. The aim of this study is to determine the p53, N- and K-ras, and beta-catenin status in this lymphoma in relation to EBV status and clinical features. The study group consisted of 32 Japanese patients with nasal NK/T-cell lymphoma. The p53 and beta-catenin expression, phenotype, and EBV-oncogenic protein latent membrane protein type 1 (LMP-1) were determined by immunoperoxidase staining. The presence of EBV-encoded small nuclear early region (EBER) RNA was determined by in situ hybridization. The p53 mutations (exons 5 to 9), N- and K-ras mutations (exons 1 and 2), and beta-catenin mutations (exon 3) were analyzed by direct sequencing of the PCR-amplified products that were obtained from laser-microdissected tissues. CD56, CD43, and CD3 were expressed in 32 (100%), in 31 (96%), and in 18 (56%) tumors, respectively. EBER RNA was detected in 31 (96%) tumors. LMP-1 was expressed in 15 (48%) tumors, and p53 and beta-catenin protein were overexpressed in 18 (56%) and 4 (13%) tumors, respectively. Six mutations of the p53 gene, 1 mutation of each N- and K-ras gene, and 8 mutations of beta-catenin gene were detected in 6 (19%), 1 (3%), and 5 (16%) tumors, respectively. The p53 missense mutation was associated with LMP-1 expression (P = 0.038), but not with p53 overexpression. Kaplan-Meier analysis as well as univariate analysis using Cox proportional hazards model showed that high lactate dehydrogenase (LDH) level (P = 0.009, P = 0.0100, respectively), large cell, immunoblastoid polymorphous histology (P = 0.005, P = 0.0162, respectively), and p53 missense mutations (P = 0.021, P = 0.0342, respectively) were significantly related to worse cause-specific survival. Multivariate analysis showed that p53 missense mutation was the most independent among these 3 factors. Although the incidence of thep53, N- and K-ras, and beta-catenin gene mutations is not high, p53 missense mutation has a prognostic value for aggressive course in nasal NK/T-cell lymphoma.
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PMID:P53, N- and K-Ras, and beta-catenin gene mutations and prognostic factors in nasal NK/T-cell lymphoma from Hokkaido, Japan. 1474 29

Lymphoepithelioma-like carcinoma of the bladder is an uncommon neoplasm, of which 49 cases have been described in the English literature, none of which has been studied for p53 protein expression. We studied three muscle-infiltrating cases of this tumor using immunohistochemical, in situ hybridization and polymerase chain reaction (PCR) methods. The three cases were positive for epithelial markers and negative for lymphoid antigens in the tumoral syncytial areas. The intensive infiltrate of small cells was negative for epithelial and positive for lymphoid markers. This population was mainly made up of cytotoxic T-lymphocytes, positive for TIA-1. p53 protein was intensely positive in more than 90% of the epithelial component nuclei, being negative in the lymphoid cells. PCR study did not show mutations on p53. Both lymphocytes and epithelium were negative for Epstein-Barr virus markers, such as the latent membrane protein and EBER (Epstein-Barr-encoded RNA). The prognosis was very good after radiotherapy and chemotherapy treatment, preserving the bladder despite the muscle infiltration. The presence of an intense cytotoxic T-lymphocyte population may be related to this good prognosis. Both aspects, p53 protein status and T-lymphoid population, had never been studied before in bladder lymphoepithelioma-like carcinoma.
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PMID:Lymphoepithelioma-like carcinoma of the bladder: three cases with clinicopathological and p53 protein expression study. 1506 46

The tumour suppressor activity of the p53 protein has been explained by its ability to induce apoptosis in response to a variety of cellular stresses. Thus, understanding the mechanism by which p53 functions in the execution of cell death pathways is of considerable importance in cancer biology. Recent studies have indicated that p53 has a direct signalling role at mitochondria in the induction of apoptosis, although the mechanisms involved are not completely understood. Here we show that, after cell stress, p53 interacts with the pro-apoptotic mitochondrial membrane protein Bak. Interaction of p53 with Bak causes oligomerization of Bak and release of cytochrome c from mitochondria. Notably, we show that formation of the p53-Bak complex coincides with loss of an interaction between Bak and the anti-apoptotic Bcl2-family member Mcl1. These results are consistent with a model in which p53 and Mcl1 have opposing effects on mitochondrial apoptosis by interacting with, and modulating the activity of, the death effector Bak.
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PMID:Mitochondrial p53 activates Bak and causes disruption of a Bak-Mcl1 complex. 1512 64

Pathogens exploit host machinery to establish an environment that favors their propagation. Because of their pivotal roles in cellular physiology, protein degradation pathways are common targets for viral proteins. Protein-linking integrin-associated protein and cytoskeleton 1 (PLIC1), also called ubiquilin, contains an amino-terminal ubiquitin-like (UBL) domain and a carboxy-terminal ubiquitin-associated (UBA) domain. PLIC1 is proposed to function as a regulator of the ubiquitination complex and proteasome machinery. Kaposi's sarcoma-associated herpesvirus (KSHV) contains a small membrane protein, K7, that protects cells from apoptosis induced by various stimuli. We report here that cellular PLIC1 is a K7-interacting protein and that the central hydrophobic region of K7 and the carboxy-terminal UBA domain of PLIC1 are responsible for their interaction. Cellular PLIC1 formed a dimer and bound efficiently to polyubiquitinated proteins through its carboxy-terminal UBA domain, and this activity correlated with its ability to stabilize cellular I kappa B protein. In contrast, K7 interaction prevented PLIC1 from forming a dimer and binding to polyubiquitinated proteins, leading to the rapid degradation of I kappa B. Furthermore, K7 expression promoted efficient degradation of the p53 tumor suppressor, resulting in inhibition of p53-mediated apoptosis. These results indicate that KSHV K7 targets a regulator of the ubiquitin- and proteasome-mediated degradation machinery to deregulate cellular protein turnover, which potentially provides a favorable environment for viral reproduction.
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PMID:Kaposi's sarcoma-associated herpesvirus K7 protein targets a ubiquitin-like/ubiquitin-associated domain-containing protein to promote protein degradation. 1508 87

We report a case of composite lymphoma consisting of peripheral T-cell lymphoma and an anaplastic variant of diffuse large B-cell lymphoma (DLBCL) and associated with Epstein-Barr virus (EBV) infection and strong p53 expression. A 65-year-old Japanese woman developed fever and generalized lymphadenopathy. A biopsy of the cervical node revealed the morphology of malignant lymphoma with 2 kinds of lymphoma coexisting in 1 lymph node. One lymphoma type consisted of immunoblastic large cells with the T-cell marker phenotype CD3+, CD45RO/UCHL-1+, CD20/L26-, CD79-, CD10-, CD30-, and CD15-; the other type consisted of large cells with abundant cytoplasm and pleomorphic nuclei with the marker phenotype CD79+, CD20/L26+, CD45RO/UCHL-1-, CD3-, CD10-, CD30+, NPM/ALK-, and CD15-. Therefore, the diagnosis was composite lymphoma of peripheral T-cell lymphoma and an anaplastic variant of DLBCL, stage IVB, because the patient had bone marrow involvement with peripheral T-cell lymphoma. The biopsy led to findings of latent type II EBV-associated lymphoma in both the peripheral T-cell lymphoma and the anaplastic variant of DLBCL as the result of positive signals for EBV small RNAs by in situ hybridization, positive immunostaining results for EBV latent membrane protein 1 antibody, and negative immunostaining results for EBV nuclear antigen 2. Immunostaining of the mass with p53 antibody also yielded positive results for both types of lymphoma cells. This case suggests that the immunocompromised state of this patient with EBV-related peripheral T-cell lymphoma allowed the emergence of an EBV-related anaplastic variant of DLBCL and suggests a close relationship between p53 expression and latent EBV infection.
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PMID:Epstein-Barr virus-associated composite lymphoma composed of peripheral T-cell lymphoma and an anaplastic variant of a diffuse large B-cell type of non-Hodgkin's lymphoma and strongly expressing p53 protein. 1516 95

Post-translational modifications (PTMs) are known to regulate biological processes by controlling protein function. The effect of a PTM on protein function depends critically on the position and the number of modifications. While there are convenient methods available to qualitatively examine modifications like phosphorylation, glycosylation, acetylation and methylation, methods available for their quantitative assessment are cumbersome. We have developed a new tool that allows quantitation of the number of phosphorylation events in proteins with ease. The "ProteoMod" tool depends on shifts in the isoelectric points of proteins upon post-translational change. The extent of shift exhibited upon phosphorylation is algorithmically converted into the number of phosphorylations conferred. The validity of ProteoMod was confirmed by examining proteins with previously known number of phosphorylations. The list of proteins examined included HSP27, HSP70 and tumor suppressor p53. The approach can also be applied to estimate modifications like acetylation, methylation and sialylation in proteins. We analyzed shifts in isoelectric points due to sialylation events in N-glycoproteins. Using influenza hemagglutinin we show that shifts in isoelectric points correlate with intracellular distribution of this model membrane protein. In addition to extending the application of two dimensional gel electrophoresis to quantitate modifications, our study also highlights its potential use in cell biology.
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PMID:ProteoMod: A new tool to quantitate protein post-translational modifications. 1517 36

Interactions among p53, bcl-2 and Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) in nasopharyngeal carcinoma (NPC) cells were evaluated by gene cotransfections. The data showed that bcl-2 expression was not only able to prevent the growth suppression induced by wild-type p53 but was also paradoxically able to inhibit the growth enhancement induced by mutant p53. Latent membrane protein 1 was shown to be capable of overcoming the growth inhibition induced by wild-type p53 and the synergistic cooperation with bcl-2 to enhance cellular growth. Latent membrane protein 1 could also cooperate with mutant p53 to provide a growth advantage for NPC cells. Most NPC revealed detectable overexpression of p53, and the majority of those were a wild type possibly responding to EBV infection. The coexpression of bcl-2 and LMP1 was thought to inhibit the growth suppression induced by wild-type p53 in NPC. But there was no associated expression between LMP1 and bcl-2 because we demonstrated that transfected LMP1 failed to induce bcl-2 expression in NPC cells in contrast to the findings in B cells. It is theorized that the cooperative expression of bcl-2 and LMP1 exists in the majority of NPC, while a minority of NPC have cooperative expression of LMP1 and mutant p53. Each cooperative interaction could play an important role in the development and progression of NPC.
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PMID:Cooperative interactions among p53, bcl-2 and Epstein-Barr virus latent membrane protein 1 in nasopharyngeal carcinoma cells. 1518

Most attacks of acute pancreatitis display a self-limiting course. This suggests that pancreatic acinar cells may be able to protect themselves against cellular injury thus preventing further progression of the disease. In this review we describe several genes overexpressed in acute experimental pancreatitis which take part in the pancreatic stress response. We discuss the possible function of the pancreatitis-associated protein 1, the small nuclear protein p8, the glycoprotein clusterin, different heat shock proteins, the p53-dependent stress proteins TP53INP1alpha and TP53INP1beta, the vacuole membrane protein-1, as well as the interferon-inducible protein-15, the antiproliferative p53-dependent protein PC3/TIS21/BTG2, and the pancreatitis-induced protein-49. The implications of these proteins in pathophysiological processes like apoptosis regulation, regeneration, cell cycle and growth control, regulation of inflammation, and vacuole formation are discussed. Study of the function of stress proteins expressed in response to pancreatitis could widen our understanding of the pathophysiology of the disease and enable us to develop new rational therapeutic strategies.
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PMID:The stress response of the exocrine pancreas. 1575 6

The latent membrane protein 1 (LMP1) of Epstein-Barr virus (EBV), a viral oncogene, is essential for transformation of resting B cells by the virus. We previously demonstrated that LMP1 could repress DNA repair in p53-wild-type and p53-deficient human epithelial cells. In this study, using a host cell reactivation (HCR) assay, we demonstrated that p53-enhanced DNA repair was repressed by LMP1 in p53-deficient cells. Moreover, we found that LMP1 was able to repress p53-dependent transcriptional activity. Regarding the mechanisms of p53 repression by LMP1, we found that LMP1 did not inhibit p53 function through direct interaction, by promoting protein degradation or reducing its DNA-binding ability. Using chimeric proteins in the reporter assay, we demonstrated that LMP1 inhibited p53 transactivation by influencing the N-terminal transactivation domain of p53. Subsequent experiments using various LMP1 deletion mutants indicated that a C-terminus-activating region of LMP1, CTAR1 or CTAR2, is responsible for the repression of p53-mediated DNA repair and p53-dependent transcription, which is correlated with the region responsible for NF-kappaB activation. Furthermore, blockage of NF-kappaB signalling by IkappaB-DeltaN was shown to abolish the repression of p53 by LMP1, suggesting that LMP1 likely repressed p53 function through the NF-kappaB pathway. Based on these results, we propose that inhibition of p53-dependent transcriptional activity and DNA repair by LMP1 results in the loss of p53 activity for maintaining genomic stability, which may contribute to the oncogenesis of LMP1 in human epithelial cells.
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PMID:Epstein-Barr virus latent membrane protein 1 represses p53-mediated DNA repair and transcriptional activity. 1582 76

The aim of this study was to discuss the relevance of the Epstein-Barr virus (EBV) in the nasopharyngeal carcinoma (NPC), analyzing the variations of several molecules potentially involved in the pathogenesis of this cancer. EBV was detected in all the NPC samples by several techniques including PCR, in situ hybridization, and immunohistochemical methodologies. CD21 membrane receptor was absent after EBV infection, being a differential morphological feature of the tumoral cells. Latent membrane protein-1 (LMP1), an oncogenic viral product, was detected in a high percentage of samples, supporting a role for EBV in the pathogenesis of NPC. Bcl-2, an anti-apoptotic protein up-regulated by LMP1, was also overexpressed, coinciding with the majority of samples positive for LMP1. Finally, p53 presented abnormalities only in a low percentage of samples. These results reinforce the role of the EBV in the NPC discussing several potential mechanisms of pathogenesis in this neoplasia.
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PMID:Involvement of the Epstein-Barr virus in the nasopharyngeal carcinoma pathogenesis. 1596 73


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