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 established conditions to efficiently differentiate embryonic carcinoma stem cells of the line P19 into myogenic cells. As inducers for differentiation, a combination of embryoid body formation in conjunction with treatment with dimethyl sulfoxide and retinoic acid proved to be most efficient. Under these conditions we detected an accumulation of myosin- and actin-specific RNA. Also, large amounts of type IV collagen RNA were produced. Type IV collagen is a component of the muscle basement membrane. In analogy to the F-9 system, we found a drastic decrease in stable p53 mRNA under the differentiation conditions used.
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PMID:An embryonal carcinoma cell line as a model system to study developmentally regulated genes during myogenesis. 608 64

Inactivation of the tumour suppressor gene lethal(2) giant larvae (D-lgl) of Drosophila leads to malignant transformation of the presumptive adult optic centers in the larval brain and tumours of the imaginal discs. These malignancies result from the disorganization of a cytoskeletal network in which the D-LGL protein participates. Here we describe the isolation of a cDNA encoding the human homologue to the D-lgl gene designated as hugl. The hugl cDNA detects a locus spanning at least 25 kilobases (kb) in human chromosome band 17p11.2-12, which is centromeric to the p53 gene and recognizes a 4.5 kb RNA transcript. The hugl gene is expressed in brain, kidney and muscle but is barely seen in heart and placenta. Sequence analysis of the hugl cDNA demonstrates a long open reading frame, which has the potential to encode a protein of 1057 amino acids with a predicted molecular weight of 115 kDaltons (kD). To further substantiate and identify the HUGL protein, we have prepared polyclonal rabbit antibodies against synthetic peptides corresponding to the amino and carboxyl termini of the conceptual translation product of the hugl gene. The affinity-purified anti-HUGL antibodies recognize a single protein with an apparent molecular weight of approximately 115 kD. Similar to the Drosophila protein, HUGL is part of a cytoskeletal network and, is associated with nonmuscle myosin II heavy chain and a kinase that specifically phosphorylates HUGL at serine residues.
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PMID:A human homologue of the Drosophila tumour suppressor gene l(2)gl maps to 17p11.2-12 and codes for a cytoskeletal protein that associates with nonmuscle myosin II heavy chain. 754 63

An inflammatory cardiomyopathy may develop in humans and experimental animals with chronic Trypanosoma cruzi infection (Chagas' disease). Among the possible mechanisms involved in the pathogenesis of Chagas' cardiomyopathy, induction of heart-specific autoimmune responses has recently received substantial experimental support. The goal of the current study was to determine whether cardiac Ag-specific antibodies are produced in T. cruzi-infected mice with heart disease and, if so, to determine their Ag specificities. Upon infection with the Brazil strain of T. cruzi, C57BL/6 mice develop a cardiomyopathy that is histologically similar to that observed in chronically infected humans. Antisera from these mice were found to react with three cardiac Ag, having relative molecular masses of 200, 150, and 53 kDa. p200 and p150 are specifically found in heart muscle, although p53 is found in skeletal muscle as well. C57BL/6 mice infected with the Guayas strain of T. cruzi, which do not develop cardiomyopathy, did not produce antibodies to p200, p150, or p53, indicating that these antibodies may be specific markers of cardiomyopathy. Finally, p200 and p53 were identified as the contractile protein myosin and the intermediate filament protein desmin, respectively. This last finding is of special interest, because antibodies specific for myosin or desmin have been detected in humans and experimental animals with other natural and experimental cardiomyopathies. This suggests that infection with particular strains of T. cruzi may lead to the development of a cardiac Ag-specific autoimmune disease, possibly involving one or more of the Ag identified in this study.
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PMID:Cardiac antigen-specific autoantibody production is associated with cardiomyopathy in Trypanosoma cruzi-infected mice. 830 Nov 48

The senescent cell-derived inhibitor (sdi)-1 (p21) protein has been identified as a downstream mediator of the tumor suppressor p53 in the cell cycle regulation. In this study, we focused on the function of sdi-1 gene in inhibiting vascular smooth muscle cell (VSMC) proliferation after vein grafting in a rabbit model. To test the hypothesis, we transfected human sdi-1 gene by an intra-operative approach. Accompanied by markedly increased sdi-1 protein, the significant increase in PCNA-stained VSMCs in vein grafts was inhibited by transfection of sdi-1 gene. Moreover, at 2 weeks after transfection, transfer of sdi-1 gene resulted in a significant inhibition in neointimal formation, compared with control vector. Of importance, immunohistological studies determining the expression pattern of myosin heavy isoforms, adult type specific SM2 and embryonic specific SMemb/NMHC-B, demonstrated expression of the adult phenotype of VSMCs in the neointima of sdi-1 gene-transfected vein grafts at 2 weeks after the operation, while the neointima was predominantly composed of embryonic phenotype of VSMCs in the control grafts. Overall, these results demonstrate that a single intraluminal incubation of human sdi-1 gene can result in a significant inhibition of neointimal formation after vein grafting, associated with phenotypic change of VSMCs from neonatal to adult type in a rabbit model. Inhibition of hyperplasia in a graft model by transfection of sdi-1 gene may be due to the change in VSMC phenotype from neonatal to adult, in addition to the inhibition of VSMC growth.
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PMID:Inhibition of intimal hyperplasia after vein grafting by in vivo transfer of human senescent cell-derived inhibitor-1 gene. 974 56

This study was designed to identify the immunophenotypic characteristics of malignant soft tissue tumours, induced experimentally with benzo(a)pyrene (BaP), and to evaluate the immunohistochemical expression of the ras oncogene family and p53 onco-suppressor gene in these tumours, in association with prognostic factors. Seventy-five male Wistar rats were subcutaneous injected, dorsally, with a single dose of 10.08 mgr BaP. A solid, well-circumscribed tumour was formed at the injection site, in 70 of the animals, 80-100 days after the carcinogen's administration. The tumour as well as selected main organs were excised and studied after the animals' death. All the specimens were fixed in formalin 10%, embedded in paraffin and stained with H + E. The immunohistochemical avidin-biotin method was performed in the tumour sections, using the following monoclonal or polyclonal antibodies: vimentin, desmin, muscle specific actin (MSA), a-smooth muscle actin (SMA), myoglobin, smooth muscle myosin, a-1-antitrypsin, a-1-antichymotrypsin, S-100 protein, epithelial membrane antigen (EMA), K-ras, H-ras, Pan-ras and p53. The induced tumours of the animals were almost well-circumscribed, with a partly storiform cut surface. Histologically, their appearance was more conventional with high grade leiomyosarcomas; about half of them showed highly anaplastic areas, resembling other pleomorphic undifferentiated sarcomas. Pulmonary metastatic foci were detected in 37 animals. Immunohistochemically, all the tumours displayed positive expression of vimentin, MSA and SMA. Desmin was positively expressed in 40 tumours, smooth muscle myosin in 57 tumours and EMA in 12 tumours. All the tumours were negative for myoglobin, a-1-antitrypsin, a-1-antichymotrypsin and S-100 protein. In addition, five tumours showed a positive reaction for K-ras p21, 37 for H-ras p21, 41 for Pan-ras p21 and 14 for p53 protein. The overexpression of the oncoproteins H-ras p21 and Pan-ras p21 in these tumours was significantly associated with a non-advanced tumour stage (absence of metastatic focus). In conclusion, the histological as well as the immunophenotypic features of the induced tumours are more conventional with leiomyosarcomas mostly of high grade; many of them are "dedifferentiated". The identification of both ras and p53 gene products in these tumours indicates that alterations of these genes are common but not specific events, implicated in the tumourigenesis, which may become prognostic markers for this subtype of soft tissue sarcomas.
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PMID:Immunophenotype, ras oncogenes and p53 onco-suppressor gene in benzo(a)pyrene induced malignant soft tissue tumours in Wistar rats. 982 59

Gene transcripts differentially expressed in activin-induced human prostatic LNCaP apoptotic cells have been discovered by an improved subtractive hybridization method, uracil-DNA subtraction assay (USA), which involves digestion with uracil-DNA glycosylase and mung-bean nuclease. Among the five up-regulated and seven down-regulated genes, we have identified six known (>95% homology and similar size; p16, p53, Siva, RHAMM, Pax2, and eIF-4a1), three homologues (>95% homology but different size; myosin, a helicase motif, and a kinase motif), and three novel genes (no homology). In addition, anti-sense knock-out of a resulting novel kinase-like gene was found to abolish the apoptotic DNA fragmentation in activin-treated LNCaP cells. These findings indicate a new potential mechanism in DNA fragmentation of activin-induced cell-cycle arresting and apoptosis.
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PMID:Differentially expressed genes in activin-induced apoptotic LNCaP cells. 1009 31

High rates of vascular smooth muscle cell (SMC) replication are observed, at least transiently, after injury to the arterial wall and contribute to the formation of a neointima. Neutralizing antibodies designed to inhibit growth of SMC have only been variably successful in inhibiting neointima formation, raising the possibility that neointimal cell proliferation involves unique growth mechanisms. This study examined the possibility that SMC isolated from injured rat carotid arteries would express an autonomous, mitogen-independent growth phenotype similar to that utilized by embryonic vascular SMC during periods of rapid growth. We found that primary cultures of SMC isolated 7 and 14 days after injury, times at which high in vivo replication rates were observed, demonstrated high intrinsic DNA synthetic rates compared to SMC isolated from uninjured arteries or at 2, 4, 21, and 28 days after injury where in vivo replication rates were far less. Subcultured SMC isolated from 7-day injured vessels (Neo7 SMC) exhibited a stable, autonomous growth phenotype, did not secrete detectable mitogenic activity, and had decreased alpha-actin and myosin expression compared to mitogen-dependent SMC. Heterokaryons constructed between autonomous Neo7 SMC and mitogen-dependent SMC exhibited a mitogen-dependent growth phenotype suggesting that nonautonomous SMC produce factors that actively inhibit autonomous growth. In contrast, heterokaryons constructed between Neo7 SMC and autonomous embryonic SMC retained an autonomous growth phenotype. We examined the expression of known tumor suppressors to determine if any of these factors played a role in inhibiting SMC autonomous growth. p27, p53, pRb, and PTEN were abundantly expressed by Neo7 SMC and e17 SMC under both basal and serum stimulated conditions. The data suggest that the mechanisms driving SMC replication during neointimal formation are self-driven and self-regulated, and that at specific times after injury, SMC escape normal growth suppressive mechanisms through the loss of intracellular growth suppressor activity.
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PMID:Transient reexpression of an embryonic autonomous growth phenotype by adult carotid artery smooth muscle cells after vascular injury. 1056 12

Experimentally elevated levels of S100A4 induce a metastatic phenotype in benign mammary tumour cells in vivo. In humans, the presence of S100A4 in breast cancer cells correlates strongly with reduced patient survival. Potential interacting binding partners for S100A4 have now been examined using an optical biosensor. There was significant interaction of S100A4 with non-muscle myosin and p53, but not with actin, tropomyosin or tubulin. The results suggest that myosin and p53 are likely to be intracellular targets of S100A4. S100A4 had a greater affinity for wild-type or mutant arg-175-his p53 than for non-muscle myosin. The results suggest that S100A4 might induce metastasis by influencing the function of p53 as well as through its interaction with myosin and that any mechanism is independent of the mutational status of p53.
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PMID:Binding to intracellular targets of the metastasis-inducing protein, S100A4 (p9Ka). 1152 29

Metastasis-associated protein S100A4 (Mts1) induces invasiveness of primary tumors and promotes metastasis. S100A4 belongs to the family of small calcium-binding S100 proteins that are involved in different cellular processes as transducers of calcium signal. S100A4 modulates properties of tumor cells via interaction with its intracellular targets, heavy chain of non-muscle myosin and p53. Here we report identification of a new molecular target of the S100A4 protein, liprin beta1. Liprin beta1 belongs to the family of leukocyte common antigen-related (LAR) transmembrane tyrosine phosphatase-interacting proteins that may regulate LAR protein properties via interaction with another member of the family, liprin alpha1. We showed by the immunoprecipitation analysis that S100A4 interacts specifically with liprin beta1 in vivo. Immunofluorescence staining demonstrated the co-localization of S100A4 and liprin beta1 in the cytoplasm and particularly at the protrusion sites of the plasma membrane. We mapped the S100A4 binding site at the C terminus of the liprin beta1 molecule between amino acid residues 938 and 1005. The S100A4-binding region contains two putative phosphorylation sites by protein kinase C and protein kinase CK2. S100A4-liprin beta1 interaction resulted in the inhibition of liprin beta1 phosphorylation by both kinases in vitro.
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PMID:Liprin beta 1, a member of the family of LAR transmembrane tyrosine phosphatase-interacting proteins, is a new target for the metastasis-associated protein S100A4 (Mts1). 1183 60

We ectopically expressed the transcription factor Pitx2a, one of the Pitx2 isoforms, in HeLa cells by using a tetracycline-inducible expression system and examined whether Pitx2a was capable of modulating Rho GTPase signaling and altering the cell's cytoskeleton. Ectopic expression of Pitx2a induced actin-myosin reorganization, leading to increased cell spreading, suppression of cell migration, and the strengthening of cell-cell adhesion, marked by the accumulation and localization of beta-catenin and N-cadherin to the sites of cell-cell contacts. Moreover, Pitx2a expression resulted in activation of the Rho GTPases Rac1 and RhoA, and the dominant negative Rac1 mutant N17Rac1 inhibited cell spreading and disrupted localization of beta-catenin to the sites of cell-cell contacts. Both reorganization of actin-myosin and cell spreading require phosphatidylinositol 3-kinase activity, which is also necessary for activation of the Rho GTPase proteins. Pitx2a induced the expression of Trio, a guanine nucleotide exchange factor for Rac1 and RhoA, which preceded cell spreading, and the expression of Trio protein was down-regulated after the changes in cell spreading and cell morphology were initiated. In addition, Pitx2a also induces cell cycle arrest at G0/G1, most likely due to the accumulation of the tumor suppressor proteins p53 and p21. Our data indicate that the transcriptional activities initiated in the nucleus by Pitx2a result in profound changes in HeLa cell morphology, migration, and proliferation.
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PMID:Pitx2a expression alters actin-myosin cytoskeleton and migration of HeLa cells through Rho GTPase signaling. 1185 22


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