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)

Induction of differentiation in M1 myeloid leukemic cells by the hematopoietic cytokines interleukin 6 and granulocyte-colony stimulating factor, or by the glucocorticoid dexamethasone, was associated with down-regulation of the apoptosis inhibiting gene bcl-2. The cytokine treated leukemic cells showed an increased sensitivity to induction of apoptotic cell death by the cancer chemotherapy compounds Adriamycin and cytosine arabinoside and by heat shock and cycloheximide. Dibutyryl cyclic AMP neither induced differentiation nor down-regulated bcl-2 expression, but it sensitized the cells to induction of apoptosis by some of these agents. Although dexamethasone induced differentiation and down-regulated bcl-2 expression, it did not sensitize the cells to induction of apoptosis and inhibited the apoptosis sensitizing effect of the cytokines and dibutyryl cyclic AMP. Dexamethasone did not inhibit induction of apoptosis by wild-type p53 or viability factor withdrawal. The apoptosis sensitizing effect of the cytokines and dibutyryl cyclic AMP was reversible upon their withdrawal.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Control of sensitivity to induction of apoptosis in myeloid leukemic cells by differentiation and bcl-2 dependent and independent pathways. 751 74

The expression of bcl-2 and p53 was investigated by immunocytochemistry in combination with that of conventional structural and differentiation antigens on the archival material of 22 cases of undifferentiated carcinoma (UC) and 19 of poorly differentiated carcinoma (PDC) of the thyroid gland. The restriction of bcl-2 expression to PDC in comparison to UC was 84.2% versus 13.6% of cases, respectively, in contrast to an almost equal percentage of p53 expression in the two histologic types, that is, 52.6% and 54.5% of cases of PDC and UC, respectively. However, the pattern of distribution of p53-immunoreactive cells was definitely different, being restricted to areas showing active infiltrating growth in PDC and involving almost all tumor cells in UC. Furthermore, in the subset of cases of UC showing the residual presence of a differentiated component, a distinctive mutual exclusion of bcl-2 and p53 immunoreactivity was observed in the two components. The results suggest that the evaluation of bcl-2 expression may be usefully applied to the differentiation of PDC from UC, whereas all morphologic findings related to p53 expression are in keeping with a significant role of the deregulation of this gene in the mechanism of dedifferentiation and progression of the disease.
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PMID:A novel panel of antibodies that segregates immunocytochemically poorly differentiated carcinoma from undifferentiated carcinoma of the thyroid gland. 752 12

Human autoimmune diseases share the common feature of an imbalance between the production and destruction of various cell types including lymphocytes (SLE), synovial cells (RA), and fibroblasts (scleroderma). Patients with SLE have increased levels of soluble Fas that inhibit proper apoptosis of lymphocytes. In animal models of autoimmune diseases, mutations of genes involved in apoptosis including Fas, Fas ligand, and the hematopoietic cell phosphatase gene have been identified. Oncogenes, including bcl-2, p53, and myc, that regulate apoptosis are also expressed abnormally. Potent inducers of apoptosis including steroids, azathioprine, cyclophosphamide, and methotrexate are the most efficacious therapies for autoimmune disease currently known. Specific therapies that induce apoptosis without incurring side effects should improve treatment of autoimmune disease.
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PMID:Autoimmune disease. A problem of defective apoptosis. 752 7

We describe the properties of a physiological cell death (PCD)-resistant subline of WEHI-231 generated from the PCD-susceptible WEHI-231.7 JM cell line maintained in our laboratory. The PCD-resistant WEHI-231.7 JMRE subline was uniquely resistant to anti-immunoglobulin (Ig)M-induced PCD but not to irradiation and etoposide. In these sublines, we compared the expression of genes implicated in regulating PCD. Northern analysis of c-myc, c-fos, egr-1, Fas, p53 and retinoblastoma revealed similar basal levels of expression in all sublines tested and comparable responses to anti-IgM treatment. Similarly, the expression of bcl-2, bcl-x, bax and IL-1 beta converting enzyme did not correlate with susceptibility to anti-IgM-induced PCD. Next, we systematically studied signal transduction events including: tyrosine phosphorylation, Ca++ flux, and ceramide production in the Jm and JMRE sublines. The tyrosine phosphorylation patterns and the Ca++ influx generated following sIgM engagement were very similar in the JM and JMRE sublines. In contrast, the generation of ceramide differed in the PCD-resistant and PCD-susceptible sublines. Ceramide is produced following cross-linking sIgM on WEHI-231.7 JM cells and causes PCD. Ceramide levels in anti-IgM-treated WEHI-231.7 JMRE cells are low and appear to be insufficient to induce PCD.
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PMID:Resistance to anti-IgM-induced apoptosis in a WEHI-231 subline is due to insufficient production of ceramide. 753 68

Diffuse large B cell lymphomas (DLBLs) represent a heterogeneous collection of aggressive non-Hodgkin's lymphomas that can arise either de novo or as a result of transformation from chronic lymphocytic leukemia, small lymphocytic lymphoma, follicular lymphomas, or lymphomas of mucosa-associated lymphoid tissue. A small percentage of DLBLs express the CD5 antigen. The majority of these cases have evolved from a pre-existing low grade non-Hodgkin's lymphoma (Richter's syndrome). However, we identified and characterized nine CD5-positive DLBLs in which the patients did not have a previous history or concomitant evidence of chronic lymphocytic leukemia, small lymphocytic lymphoma, follicular lymphoma, or mucosa-associated lymphoid tissue-associated non-Hodgkin's lymphoma, suggesting that they arose de novo. All nine cases expressed CD20 and monotypic immunoglobulin, all eight cases examined expressed CD19, CD22 and CD43, eight of the nine cases expressed HLA-DR, and two of eight cases expressed CD11c. None of the cases expressed CD3, CD10, CD11b, CD21, CD23 or CD30. CD5 expression by these cells was found to be identical to that of CD5-positive B cell chronic lymphocytic leukemia by quantitative polymerase chain reaction analysis of CD5 mRNA. These nine de novo CD5-positive DLBLs exhibited clonal immunoglobulin heavy and light chain gene rearrangements but lacked integration of the Epstein-Barr virus genome and structural alterations of the bcl-1, bcl-2, c-myc, H-ras, K-ras, and N-ras proto-oncogenes and the p53 tumor suppressor gene. However, bcl-6 proto-oncogene rearrangement, which is involved in chromosome band 3q27 aberrations, was found in four cases (44.4%). This is comparable with the frequency of bcl-6 gene rearrangement in CD5-negative DLBL. In contrast, bcl-6 gene rearrangement was absent in six cases of DLBL associated with Richter's syndrome. These findings suggest that de novo CD5-positive DLBLs are genotypically similar to CD5-negative DLBLs and may be pathogenetically distinct from the DLBLs associated with Richter's syndrome.
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PMID:De novo CD5-positive and Richter's syndrome-associated diffuse large B cell lymphomas are genotypically distinct. 754 11

Hypothetical Products from Noncoding Frames (i.e., HyPNoFs) are hypothetical, not-coded proteins, translated from alternate reading frames (i.e., coding + 1 and coding + 2) of cDNAs. HyPNoFs of CD4, PKC, oncostatin, bcl-2 proto-oncogene, tumor suppressor p53, cystic fibrosis transmembrane regulator (CFTR), and tumor necrosis factors alpha and beta were searched as query sequences vs the SWISS-PROT data bank. Homology searchers carried out revealed that hypothetical products (i.e., HyPNoFs) may share high similarity with real protein products actually coded. Sequence similarity of hypothetical products to real proteins is sometimes very high, suggesting common conformational features, according to the Sander and Schneider cutoff value. This finding supports the hypothesis that eukaryotic DNA, currently considered to be monocistronic, might occasionally have polycistronic regions, carrying different protein messages on overlapping frames. As yet, polycistronic genes have been observed in viral genomes only. The presence of polycistronic regions in eukaryotic genes is likely reminiscent of an ancient strategy, rather than a present feature of the genome in eukaryotes. These data suggest that thorough investigation of HyPNoFs is likely to improve our ability to trace genes' evolution and to investigate structure-function relationships of protein and DNA sequences.
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PMID:Investigating hypothetical products from noncoding frames (HyPNoFs). 754 50

Anti-CD3 monoclonal antibodies (MoAbs) and glucocorticoid hormones (GCH) induce apoptosis in immature thymocytes and peripheral T lymphocytes. This process is inhibited by a number of growth factors, including interleukin-2 (IL-2), IL-3, and IL-4, indicating that signals generated by membrane receptors can modulate the survival of lymphoid cells. To investigate whether signals activated by adhesion receptors have a similar activity, we analyzed the effect of CD44 (Pgp-1) adhesion molecule receptor stimulation on T-cell apoptosis induced by three stimuli (anti-CD3 MoAbs, dexamethasone [DEX] treatment, and exposure to ultraviolet irradiation [UV]) on a 3DO T-cell line. The results show that CD44 engagement, either by hyaluronic acid (HA) or anti-CD44 MoAbs, inhibits DNA fragmentation and apoptosis induced by DEX and anti-CD3 MoAbs, whereas that induced by UV, a p53-dependent phenomenon, was not inhibited. Furthermore, the antiapoptotic effect exerted through CD44 activation does not seem related to overexpression of bcl-2 or to have appreciable effects on cell proliferation. Our results indicate that adhesion molecules modulate T-cell survival by counteracting apoptosis induced by DEX or anti-CD3 MoAbs.
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PMID:CD44 (Pgp-1) inhibits CD3 and dexamethasone-induced apoptosis. 754 65

The p53 tumor suppressor gene product, and the bcr-abl, bcl-2, and c-myc gene products all appear to influence the susceptibility of cells to apoptosis. In addition to the role p53 protein plays in mediating a cell cycle arrest in G1 following DNA damage, p53 also performs functions critical for removal of damaged cells by initiating apoptosis in certain physiological situations. Cells which express deregulated c-myc are sensitized to apoptosis following various growth suppressing stimuli and these observations have provided new insights into how apoptosis-suppressing genes such as mutant p53, bcl-2 and bcr-abl may cooperate during transformation and how they might influence the sensitivity of cells to radiation and chemotherapy.
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PMID:Induction of apoptosis by tumor suppressor genes and oncogenes. 754 37

This review attempts to provide current information on the role played by the p53 gene in normal and leukemic hematopoiesis with particular emphasis on chronic myeloid leukemia. On the basis of the currently available data we can argue that p53 acts as a negative regulator of proliferation of myeloid mature cells and CD34+ progenitors, and its action is mediated through changes in cell cycle kinetics, mainly before the S phase. The p53-dependent pathway is also regulated by several proteins, including p16, p21, p27 (cyclin-dependent kinase [CDK] inhibitors), and a few oncogenes (bcl-2, bax, MDM-2). Although there is some information about the changes in the p53 gene seen in various types of leukemia, the functions and biological importance of these changes in the pathogenesis of leukemia are still largely elusive. During the past several years, accumulated evidence suggests that changes in the p53 gene are commonly associated with blast crisis of chronic myeloid leukemia (CML) but rarely with chronic phase, and they are represented by rearrangements, deletions and point mutations. As for most of the tumors, the majority of point mutations occur between exons 4 and 8 (hot regions). In patients with CML in blastic crisis the most frequent mechanism of p53 inactivation is complete deletion of one allele in association with a point mutation in the remaining allele.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of p53 in leukemogenesis of chronic myeloid leukemia. 754 4

The tumor suppressor gene p53 regulates G1 checkpoint prior to the initiation of DNA synthesis, which can either induce G1 arrest or signal apoptosis. The involvement of p53 in apoptosis may also be related to its ability to down-regulate transcription of the bcl-2 gene. The bcl-2 gene product prevents most types of apoptotic cell death, suggesting that bcl-2 interferes with an essential signaling molecule involved in the apoptotic cell death pathway. Although the bcl-2 protein is shown to be overexpressed in many types of human tumor including breast cancer, its biochemical or pathological consequences are poorly understood. To determine the effects of bcl-2 overexpression on apoptosis and transformation of breast epithelial cells and to investigate whether bcl-2 interferes with the p53 pathway, we introduced the bcl-2 expression vector into MCF10A cells, which were derived from diploid human breast epithelial cells containing the wild-type p53 gene. Overexpression of bcl-2 prevented free radical-induced apoptosis and induced a partially transformed phenotype in MCF10A cells. Although overexpression of bcl-2 did not affect the expression of the p53 gene, p53-dependent gene transcription such as p21WAF1/CIP1 was suppressed. These results suggest that bcl-2 may inhibit p53 functional activity and is involved in the regulation of an early commitment step either to proliferate or suicide.
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PMID:bcl-2 suppresses expression of p21WAF1/CIP1 in breast epithelial cells. 755 20


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