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)

P53 is a tumour suppressor gene, located in the short arm of chromosome 17, which encodes for a nuclear protein involved in the control of cellular growth, regulating the entry of the cell into the S-phase. P53 mutations have been identified in a progressively increasing number of human malignancies. Nuclear p53 protein is usually present in non-tumour cells in minute concentrations, due to its short half-life. In contrast, tumours with p53 mRNA mutations show a higher nuclear protein concentration, detectable by immunohistological techniques, due to stabilization by complexing with other proteins such as heat-shock protein or wild-type p53 protein. Levels of nuclear p53 protein detected by immunohistochemistry with the monoclonal antibody PAb 1801 were measured with the aid of an image analysis system in 83 non-Hodgkin's lymphomas (NHLs) and 13 cases of Hodgkin's disease, as well as in 14 cases of normal thymus, reactive tonsils, and lymphadenitis. High levels of p53 protein (greater than 5 per cent of the cells) were present only in high-grade lymphomas (in the proportion 13/55), with a peak incidence in Burkitt's lymphoma (5/8 cases). Lower levels (less than 5 per cent) of p53 protein were detected in low-grade B- and T-cell lymphomas, as well as in most of the cases of Hodgkin's disease, where p53 protein was selectively present in Hodgkin and Reed-Sternberg cells. In 5/14 reactive tonsils or lymph nodes, occasional p53-positive cells were identified. These results suggest a relationship between levels of p53 protein and the aggressiveness of NHL.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:P53 protein expression in lymphomas and reactive lymphoid tissue. 138 24

HHV-6 infected immature T (HSB2) and Hodgkin (HDLM2) cells and biopsy tissues from lymph nodes of patients with Hodgkin's disease (HD) and Kikuchi lymphadenitis (KL) were studied immunohistologically for virus antigen expression and for the oncogene/anti-oncogene products ras, bcl-2 and p53. Cell proliferation and cell death were tentatively monitored in tissue culture by PCNA staining, by viability testing and in situ end labeling of fragmented DNA. PCNA was also used in biopsy samples. KL is characterized by high incidences of focal cell death (i.e. histiocytic necrotizing lymphadenitis), while HD is apparently more a proliferative disease. The techniques used revealed no significant differences in the cellular expression of viral DNA or antigens among cell lines, HD or KL. The HDLM2 cell line with the superior survival after HHV-6 infection showed a significantly lower expression of p53 and PCNA than HSB2 cells. Biopsy samples from patients with KL did not express p53, and ras and PCNA were observed in fewer cells than in HD. Bcl-2, however, was significantly more frequently seen than in HD. The interpretation of the data is difficult; they suggest that there are additional regulatory influences in control of cell proliferation and cell death, such as cytokines and growth factors, which are altered after viral infection. Also, virus-induced cell death probably includes other mechanisms besides apoptosis, such as cell damage caused by oxygen radicals.
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PMID:[Apoptosis and cell proliferation in HHV-6 infections. Regulatory mechanisms of p53/bcl-2/ras interactions]. 776 57

The p53 gene located in the short arm of chromosome 17 at position 17p13, is involved in the negative regulation of cellular growth. p53 mutation seems to be the most frequent genetic alteration found in human cancer. Mutant conformation of the p53 gene is associated with cell proliferation and tumour progression, and in most cases implies p53 stabilization, which renders the p53 protein detectable through the use of immunohistochemical techniques. p53 expression is a frequent finding in high grade lymphomas of either B or T cell lineage, having been detected in 30% of cases in our series. The focal presence of p53+ cells was seen in a wide range of low and high grade lymphomas, including lymphadenitis and reactive tonsils. In 37.5% of cases this increased expression of p53 was secondary to mutation in highly conserved regions (exons 5-8). Unlike findings reported in other tumours, in lymphomas, p53 expression seems to be secondary to genetic alterations other than p53 mutation. Initial data suggest that the MDM2 protein could be involved in inactivating p53 protein in most of these cases. Finally, p53 expression has been found to be a poor prognostic marker in high grade B-cell lymphomas in a large series of cases. High p53 expression was associated with a short survival, this relation being stronger in cases with simultaneous bcl2 expression.
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PMID:p53 expression in non-Hodgkin's lymphomas: a marker of p53 inactivation? 777 62

Histiocytic necrotizing lymphadenitis, also called Kikuchi-Fujimoto (KF) disease, is a benign disorder characterized histologically by paracortical necrotic foci surrounded by histiocytic aggregates. We analysed affected lymph node tissues from 34 patients with the disease in an attempt to elucidate its histogenesis. The 'necrotizing' cells showed typical apoptotic changes, including cell shrinkage and condensed and fragmented nuclei. Apoptotic bodies with a peculiar ultrastructure were demonstrated, and DNA fragmentation was detected in these cells by in situ end labelling. Immunostaining for the apoptosis-regulating proteins bcl-2, bax, c-myc and p53 failed to show their involvement in KF disease. However, perforin, a killer cell-specific cytolytic protein essential for provoking apoptosis in target cells, was found to be expressed abundantly by the infiltrating cells, which were thought to be cytotoxic T-lymphocytes. Perforin-expressing cells were present in the apoptotic foci of 28 of the 34 patients (82.4%). Virtually no cells containing perforin granules were present in non-pathological regions, lymph node tissues from control subjects with reactive or tuberculous lymphadenitis or those from patients with KF disease with negligible apoptosis. Therefore, the 'necrosis' associated with KF disease appears to be attributable to trans apoptotic death of the killer cell target in the affected nodes. We propose that KF disease should be called apoptotic lymphadenitis.
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PMID:Involvement of cell-mediated killing in apoptosis in histiocytic necrotizing lymphadenitis (Kikuchi-Fujimoto disease). 883 19

Studies have shown that BIRC7, a new member of inhibitor of the apoptosis protein family, is expressed in fetal tissues and most solid tumors in humans. However, there are no reported data concerning BIRC7 expression in lymphomas. We investigated the expression of BIRC7, survivin, Bcl-2, Bax, p53 and p170 proteins in 167 cases of non-Hodgkin's lymphoma (NHL) and 10 cases of non-specific lymphadenitis by tissue microarray-based immunohistochemistry. BIRC7 mRNA in three cell lines and 16 cases of NHL were detected by reverse transcriptase-polymerase chain reaction. BIRC7 protein was exhibited in the cytoplasm of cells in 25 (31%) of 80 cases of B-NHLs, 32 (37%) of 87 cases of T-NHLs, and none in non-specific lymphadenitis. The positive rate of BIRC7 was lower than that of survivin in almost all types of NHL with no significant differences, and similar to that of Bcl-2, Bax or p53. There was no correlation of protein expression between BIRC7 and any other detected markers, except p170 in T-NHL (P < 0.001). BIRC7 expression did not correlate with clinic pathologic factors such as sex, age, stage and grade, but overexpression of BIRC7 was positively correlated with aggression of NHL cells (P < 0.05). BIRC7 mRNA expressed in six (38%) of 16 cases of NHLs. BIRC7 mRNA expression was approximately consistent with BIRC7 protein in NHL. Our results indicate that the BIRC7 gene might play a role in the development and aggression of NHL and that the inhibition of BIRC7 expression may be important in NHL treatment.
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PMID:Expression of BIRC7 protein and mRNA in non-Hodgkin's lymphoma. 1684 Feb 3