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 expression was studied in 111 primary breast cancers with a monoclonal antibody (PAb240) that reacts with an epitope in mutant p53. Epidermal growth factor receptors (EGFr) and oestrogen receptors (ER) measured by ligand binding, c-erbB-2 expression assessed by immunochemistry and lymph node status were compared with p53 staining. Fifty-nine tumours (53%) were positive for p53, and this correlated with EGFr expression (P less than 0.02), which is a known poor prognostic factor. Eighteen out of 59 p53+ tumours expressed c-erbB-2 versus 4 out of 52 p53- tumours assessed on paraffin sections. However, assessing c-erbB-2 by Southern blotting and immunochemistry on frozen sections showed that 20 out of 59 p53+ tumours overexpressed or had amplified c-erbB-2 compared with 15 out of 52 p53- tumours (not significant). Mean EGFr concentration in p53+ tumours was 31 fmol per mg of membrane protein versus 14 fmol mg-1 in p53- tumours. Cytoplasmic staining was the most frequent pattern found for p53, but some cases showed cytoplasmic plus nuclear staining, or focal cells with predominantly nuclear staining. Thus, abnormal p53 is the commonest oncogene abnormality described in breast cancer. The association with EGFr expression suggests that these oncogenes interact in the pathogenesis of breast cancer.
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PMID:Mutant p53, EGF receptor and c-erbB-2 expression in human breast cancer. 168 17

Programmed cell death is a physiological, energy-consuming mechanism leading to suicide of the cell. Cell death is accomplished by the activation of endonucleases that fragment the cell's nuclear DNA. Some tumour cells remain susceptible to programmed death. These are hormone- and growth factor-dependent tumour cells. Hormone or growth factor deprivation induces signals leading to apoptosis. Other tumours gain strong resistance to apoptosis. One of the normal functions of the bcl-2 gene is to provide longevity to memory B cells. When this gene becomes translocated in follicular B cell lymphomas, it renders lymphoma cells resistant to apoptosis. Latent membrane protein encoded by an EBV gene, either by itself or by amplifying bcl-2, enables tumour cells (nasopharyngeal carcinoma; Reed-Sternberg cell of Hodgkin's disease) to resist apoptotic death. Loss of antioncogene p53 provides for resistance against programmed cell death. Breakdown of resistance to apoptosis in tumour cells can be achieved by oncolytic viruses; generation of lymphotoxin and tumour necrosis factor; monoclonal antibodies; transfection with plasmid vectors carrying p53; gamma irradiation; and certain chemotherapeutic agents.
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PMID:Programmed cell death (apoptosis): its virological and immunological connections (a review). 181 29

Epstein-Barr virus and the C3d fragment of the third component of complement are specific extracellular ligands for complement receptor type 2 (CR2). However, intracellular proteins that react specifically with CR2 and are involved in post-membrane signals remain unknown. We recently prepared polyclonal anti-idiotypic anti-CR2 antibodies (Ab2) by using the highly purified CR2 molecule as original immunogen. We showed that Ab2 contained anti-idiotypic specificities that mimicked extracellular domains of CR2 and detected two distinct binding sites on CR2 for its specific extracellular ligands, Epstein-Barr virus and C3d. We postulated that Ab2 might also contain specificities that could mimic intracellular domains of CR2. Here we report that Ab2, which did not react with Raji B-lymphoma cell surface components, detected specifically, among all components solubilized from Raji cell membranes, a single intracellular membrane protein of apparent molecular mass of 53 kDa. This protein was identified as the p53 cellular antioncogene-encoded membrane phosphoprotein by analyzing its antigenic properties with Pab1801, a monoclonal anti-p53 antibody, and by comparing its biochemical properties with those of p53. Additionally, solubilized and purified CR2 bound to solubilized p53 immobilized on Pab1801-Sepharose. p53, like CR2, was localized only in purified plasma membranes and nuclei of Raji cells. These data suggest strongly that p53, a cellular antioncogene-encoded phosphoprotein, reacted specifically with CR2 in Raji membranes. This interaction may represent one of the important steps through which CR2 could be involved in human B-lymphocyte proliferation and transformation.
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PMID:Epstein-Barr virus/complement fragment C3d receptor (CR2) reacts with p53, a cellular antioncogene-encoded membrane phosphoprotein: detection by polyclonal anti-idiotypic anti-CR2 antibodies. 255 14

The glycosylphosphatidylinositol (GPI)-anchored membrane protein urokinase plasminogen activator-receptor (uPA-R; CD87) is one of the key molecules involved in migration of leukocytes and tumor cells. uPA bound to uPA-R provides the cell proteolytic potential used for degradation of extracellular matrix. uPA-R is also involved in induction of cell adhesion and chemotaxis. Here, we provide a molecular explanation for these uPA-R-related cellular events. By size fractionation of monocyte lysate and affinity isolation on its natural ligand uPA, we demonstrate uPA-R as a component of a receptor complex of relatively large size. Reprecipitation and immunoblotting techniques allowed us to detect the protein tyrosine kinases (PTKs) p60fyn, p53/56lyn, p58/64hck, and p59fgr as components of this "uPA-R complex". Activation of monocytes even with enzymatically inactivated uPA resulted in induction of tyrosine phosphorylation, suggesting modulation of uPA-R-associated PTKs upon ligand binding. In spite of their presence in large complexes, we did not find the GPI-linked proteins CD14, CD58, and CD59 in the uPA-R complex, which indicates the presence of different receptor domains containing GPI-linked proteins in monocytes. However, we identified the leukocyte integrins LFA-1 and CR3 as components of the uPA-R complex as indicated by coisolation of these molecules, as well as by cocapping and comodulation of uPA-R and leukocyte integrins on the monocyte surface. The assemblage of uPA-R, PTKs and membrane spanning beta 2-integrins in one receptor complex indicates functional cooperation. In regard to the involvement of these molecules in pericellular proteolysis, signal transduction, as well as adhesion and chemotactic movement, we suggest uPA-R complex as a potential cellular device for cell migration.
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PMID:Urokinase plasminogen activator receptor, beta 2-integrins, and Src-kinases within a single receptor complex of human monocytes. 753 37

We have previously shown that exogenous wild type p53 induces apoptosis in the Burkitt lymphoma line BL41 that carries endogenous mutant p53, using a temperature sensitive p53 construct expressed as mutant p53 at 37 degrees C and wild type p53 at 32 degrees C (Ramqvist et al., Oncogene, 8, 1495-1500, 1993). We also found that wild type p53-induced apoptosis is blocked by bcl-2 in a mouse T lymphoma line (Wang et al., Oncogene, 8, 3427-3431, 1993) The Epstein-Barr virus (EBV)-encoded latent membrane protein 1 (LMP1) can protect Burkitt lymphoma cells from apoptosis induced by low serum. In order to test if LMP1 can block p53-triggered apoptosis, we infected BL41 cells expressing the ts p53 construct with an LMP1-carrying retrovirus. The LMP1-expressing BL41-ts p53 cells were arrested in G1 upon induction of wild type p53 expression at 32 degrees C, but did not enter apoptosis as shown by the absence of positive TUNEL staining. WAF1/p21 mRNA was induced at 32 degrees C in both the ts p53-expressing and ts p53/LMP1-expressing BL41 cells. Thus, LMP1 prevents p53-induced apoptosis but does not interfere with induction of WAF1/p21. The LMP1-infected cells expressed elevated bcl-2 protein levels. Therefore, our data suggest that LMP1 blocks p53-triggered apoptosis but not G1 arrest by upregulating bcl-2 expression.
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PMID:The EBV-encoded LMP1 protein inhibits p53-triggered apoptosis but not growth arrest. 756 60

Since the introduction of standardized chemotherapy protocols of osteosarcoma a lot of new aspects in prognosis and curability of these have best developed. Current subclassification which divided osteosarcoma into a conventional type and eleven important recognizable varieties is one of the reason for this success. Cytological grading also serves as a good indicator for the prognosis and is an important criterion for application of adjuvant chemotherapy. Several structure proteins of the extracellular matrix have gained importance in making the diagnosis of an osteosarcoma. Immunohistochemically and biochemically evaluations could show that different collagenous-proteins can be useful for the differential diagnosis of bone tumors. The integration of molecular pathologic methods into the structural morphologic findings will be helpfull in the identification of mutated structure proteins. Oncogenes and tumor suppressor genes are of major importance for the tumorigenesis of osteosarcoma. The prognostic significance of the inactivation of p53 and RBI gene remains to be elucidated. Resistance to chemotherapy is the major mechanism responsible for the failure of osteosarcoma treatment. The main cause for this failure is multidrug resistance, which is often related to a plasma membrane protein, the P-glycoprotein. Immunohistologic investigations of P-glycoprotein are not sufficient to demonstrate the possible association between overexpression of this protein and tumor progression.
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PMID:Current aspects of the pathology of osteosarcoma. 764 21

Five cases of intravascular lymphomatosis (IVL) are reported. Diffuse or focal cerebral signs suggestive of vascular disease occurred in four cases, but case 5 presented with symptoms similar to Creutzfeld-Jakob disease. Clinical course ranged from two to eight months and diagnosis was made in all cases by autopsy. Neoplastic lymphoid cells mainly lodged in lumina of small vessels in many organs, but infarction was confined to the CNS. Some extravascular tumor cells were regularly seen. All cases corresponded to high-grade Non-Hodgkin lymphomas of B-cell type and displayed high proliferation indices. Different from findings in primary cerebral and nodal lymphomas, neither p53 nor bcl-2 oncoproteins were detectable. Absence of EBV genome and EBV latent membrane protein from IVL was demonstrated for the first time.
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PMID:Intravascular lymphomatosis of the CNS: clinicopathologic study and search for expression of oncoproteins and Epstein-Barr virus. 798 93

Lymphoepithelial carcinoma (Schmincke's tumor) is a relatively common malignancy in the upper respiratory tract (nasopharynx), but it rarely occurs at other sites. We describe here the first case of a vaginal neoplasm that closely resembled lymphoepithelial carcinoma in its histological features and immunophenotype. The tumor was detected in an 81-year-old woman who presented with recurrent vaginal bleeding. On colposcopy, an ulcerated polypoid tumor mass was seen in the posterior wall of the middle portion of the vagina. Histologic examination revealed an undifferentiated spindle-cell carcinoma (KL1+, chromogranin A-, vimentin-) with abundant lymphocytes (mostly UCHL1+ T cells), plasma cells, and macrophages (CD68+) in and around the tumor cell nests. A minority of the tumor cells exhibited overexpression of p53 protein and a quarter of the tumor cells reacted with the antibody MIB1, that is, were in a proliferate state. The tumor cells did not react with the monoclonal antibody DAKO-EBV, which detects a latent membrane protein (LMP-1) encoded by the Epstein-Barr virus. The tumor underwent regression after radiotherapy. No signs of recurrence or dissemination of the carcinoma have been detected clinically during the 6 months since treatment.
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PMID:Lymphoepithelioma-like carcinoma of the vagina: a case report with special reference to the immunophenotype of the tumor cells and tumor-infiltrating lymphoreticular cells. 800 41

We have previously shown that forskolin and 3-isobutyl-1-methylxanthine (IBMX) increased accumulation of cisplatin (DDP) in DDP-sensitive 2008 human ovarian carcinoma cells in proportion to their ability to increase cAMP. Since the major function of cAMP is to activate protein kinase A, it was conjectured that the stimulation of DDP accumulation was mediated by a protein kinase A substrate. We now show that exposure of 2008 cells to forskolin resulted in phosphorylation of a prominent 52-kD membrane protein. Microsequencing of the band demonstrated it to be human beta-tubulin. Similarly, pretreatment of 2008 cells with the microtubule stabilizing drug taxol increased platinum accumulation in a dose-dependent manner. In 11-fold DDP-resistant 2008/C13*5.25 cells, decreased DDP accumulation was associated with enhanced spontaneous formation of microtubule bundles and decreased expression of beta-tubulin and the tubulin-associated p53 antioncogene relative to 2008 cells. 2008/C13*5.25 cells had altered sensitivity to tubulin-binding drugs, being hypersensitive to taxol and cross-resistant to colchicine. We conclude that pharmacologic alterations of tubulin enhance accumulation of DDP, and that the DDP-resistant phenotype in 2008/C13*5.25 cells is associated with tubulin abnormalities.
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PMID:In vitro modulation of cisplatin accumulation in human ovarian carcinoma cells by pharmacologic alteration of microtubules. 810 Aug 37

ERGIC-53 (former designation, p53) is a 53-kDa nonglycosylated, dimeric, and hexameric type I membrane protein that has been established as a marker protein for a tubulovesicular intermediate compartment in which protein transport from the endoplasmic reticulum to the Golgi apparatus is blocked at 15 degrees C. Although ERGIC-53 is not a resident protein of the rough endoplasmic reticulum its cDNA sequence carries a double lysine endoplasmic reticulum retention motif at the cytoplasmically exposed COOH terminus. Here we report that overexpression of ERGIC-53 in COS cells saturates its intracellular retention system leading to the appearance of ERGIC-53 at the cell surface. Cell surface ERGIC-53 is efficiently endocytosed by a mechanism that is disturbed when the two critical lysines of the endoplasmic reticulum retention motif are replaced by serines. The results suggest a mechanistic similarity of pre-Golgi retention by the double lysine motif and lysine-based endocytosis.
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PMID:A dual role for COOH-terminal lysine residues in pre-Golgi retention and endocytosis of ERGIC-53. 811 75


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