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Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The genetic alteration of p53 is associated with neovascularization during progression of glioma to its more malignant form, glioblastoma. Hence, one or more of the genes transactivated by p53 is likely to function as an angiogenesis inhibitors. We isolated a novel p53-inducible gene that encodes a 1584-amino-acid product containing five thrombospondin type 1 (TSP-type 1) repeats and is specifically expressed in the brain. A recombinant protein corresponding to the TSP-type 1 repeats of this gene product inhibited in vivo neovascularization induced by bFGF in the rat cornea. The expression of this gene, designated BAI1 (brain-specific angiogenesis inhibitor 1) was absent or significantly reduced in eight of nine glioblastoma cell lines, suggesting BAI1 plays a significant role in angiogenesis inhibition, as a mediator of p53.
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PMID:A novel brain-specific p53-target gene, BAI1, containing thrombospondin type 1 repeats inhibits experimental angiogenesis. 939 72

We have identified two novel human genes homologous to BAI1 (brain-specific angiogenesis inhibitor 1), an angiogenesis inhibitor that is a candidate for involvement in development of glioblastoma. Like BAI1, these two genes, designated BAI2 and BAI3, were specifically expressed in brain, and are likely to be expressed in the same type of cells. However, in spite of similar tissue specificity among the three BAI genes, only BAI1 is transcriptionally regulated by p53. BAI3 expression was absent in two of nine glioblastoma cell lines examined and was significantly reduced in three of the remaining seven. These data suggest that members of this novel gene family may play important roles in suppression of glioblastoma. BAI1, BAI2 and BAI3 were mapped to 8q24, 1p35 and 6q12, respectively.
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PMID:Cloning and characterization of BAI2 and BAI3, novel genes homologous to brain-specific angiogenesis inhibitor 1 (BAI1). 953 23

Brain-specific angiogenesis inhibitor 1 (BAI1), which is a p53-target gene specifically expressed in brain, encodes a seven-span transmembrane protein. Using a two-hybrid system, we isolated a cDNA that encodes a protein, named BAP1 (BAI1-associated protein), which interacts with the cytoplasmic region of BAI1. BAP1 is a novel member of the MAGUK (membrane-associated guanylate kinase homologue) family; it possesses a guanylate kinase domain, WW domains, and multiple PDZ domains. Interaction between BAI1 and BAP1 was mediated by a QTEV motif in the carboxy-terminal region of BAI1 and PDZ domains of BAP1. By immunocytochemical analysis of COS-7 cells transfected with BAI1 and BAP1, both products were co-localized at the cytoplasmic membrane, especially at cell-cell junctions. Cells transfected with BAI1 formed filopodia-like cytoplasmic extensions. These results suggest that BAI1 and BAP1 might be involved in cell adhesion and signal transduction in brain.
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PMID:Cloning and characterization of BAI-associated protein 1: a PDZ domain-containing protein that interacts with BAI1. 964 39

Brain-specific angiogenesis inhibitor (BAI) 1 was recently isolated as a novel p53 inducible gene. BAI1 has been suggested to play a significant role in angiostasis. We studied the expression of BAI1 in 49 colorectal cancer specimens by RT-PCR. BAI1 expression was significantly reduced in colorectal cancers as compared to the extraneoplastic tissues (X(2) test, p=0.041). BAI1 expression was inversely correlated with vascular invasion and metastasis (Fisher's exact test, p 0.045). Moreover, vascularity in the colorectal cancer was inversely correlated with BAI1 gene expression (Mann-Whitney U-test, p=0.0003). These observations suggested that BAI1 expression might inhibit angiogenesis and metastasis of colorectal cancer.
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PMID:Brain-specific angiogenesis inhibitor 1 expression is inversely correlated with vascularity and distant metastasis of colorectal cancer. 977 87

BAI1 (brain-specific angiogenesis inhibitor 1), a p53-target gene specifically expressed in brain, encodes a seven-span transmembrane protein considered to be a member of the secretin receptor family. Using a two-hybrid system, we isolated a cDNA encoding a product that interacts with the cytoplasmic region of BAI1 and designated it BAP3 (BAI1-associated protein 3). The BAP3 product is a novel C2 domain-containing molecule with homology to Munc13 and synaptotagmin. As with Munc13, BAP3 is expressed predominantly in brain. Deletion-mutant analysis revealed that the interaction between BAI1 and BAP3 was not mediated by the C2 domains. Its predominant expression in brain and homology to Munc13 indicate that BAP3, by interacting with BAI1, might be involved in some neuronal function such as regulating release of neurotransmitters.
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PMID:Cloning and characterization of BAP3 (BAI-associated protein 3), a C2 domain-containing protein that interacts with BAI1. 979 Sep 24

BAI1 (brain-specific angiogenesis inhibitor 1) was originally isolated as a p53-target gene specifically expressed in brain. To clarify its function, we have been searching for cellular proteins that associate with the cytoplasmic domain of BAI1. Using its intracellular carboxyl terminus as "bait" in a yeast two-hybrid system, we isolated a cDNA clone named BAIAP2 whose nucleotide sequence would encode a 521-amino acid protein showing significant homology to a 58/53-kDa substrate of insulin-receptor kinase in the hamster. As the expression profile of BAIAP2 examined by Northern blot analysis was almost identical to that of BAI1, BAIAP2 appears to be active mainly in neurons. In vitro binding assays confirmed that a proline-rich cytoplasmic fragment of BAI1 interacted with the Src homology 3 (SH3) domain of BAIAP2. Double-color immunofluorescent analysis revealed that BAIAP2 was localized at the cytoplasmic membrane when it was coexpressed with BAI1 in COS-7 cells; BAIAP2 not associated with BAI1 was diffused in the cytoplasm. Predominant localization of BAI1 protein in a sub-cellular fraction enriched in growth cones indicated a possible role of BAI1 as a cell adhesion molecule inducing growth cone guidance. As a protein partner of BAI1, BAIAP2 may represent an important link between membrane and cytoskeleton in the process of neuronal growth.
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PMID:Identification of BAIAP2 (BAI-associated protein 2), a novel human homologue of hamster IRSp53, whose SH3 domain interacts with the cytoplasmic domain of BAI1. 1034 8

Angiogenesis is required for the growth and progression of malignancies. Recent studies have demonstrated that genetic alterations may accompany acquisition of the angiogenic phenotype. The tumor suppressor gene p53 is most frequently mutated in human cancers and is also known to be a transcriptional regulator of a variety of genes. Here, we investigated the antiangiogenic effect of the wild-type p53 (wt-p53) gene transfer on a human non-small cell lung cancer cell line. Mutant p53-expressing H226Br non-small cell lung cancer cells were transduced with the wt-p53 gene using a recombinant adenoviral vector (Ad5CMVp53) and applied to semiquantitative reverse transcription-PCRs for the detection of altered mRNA expression of angiogenic and/or antiangiogenic factors. In vivo neovascularization assay of Ad5CMVp53-infected cells was then performed using a membrane-diffusion chamber system s.c. transplanted in nu/nu mice. We also evaluated the effect of Ad5CMVp53-infected H226Br cells on nontransduced tumor cells in vivo by s.c. inoculating mixture of cells into nu/nu mice. Ad5CMVp53 infection markedly inhibited the expression of an angiogenic factor, vascular endothelial growth factor, and increased the expression of a novel antiangiogenic factor, brain-specific angiogenesis inhibitor 1, resulting in reduced neovascularization in vivo. Mixing experiments showed that tumor cells transduced with the wt-p53 gene inhibited the in vivo tumor growth of adjacent nontransduced cells. Our data suggest that a recombinant adenovirus expressing the wt-p53 gene is antiangiogenic, which may explain, in part, the mechanism of the bystander effect induced by the wt-p53 gene transfer on adjacent tumor cells.
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PMID:Recombinant adenovirus expressing wild-type p53 is antiangiogenic: a proposed mechanism for bystander effect. 1035 34

Angiogenesis is required for the growth and progression of malignancies. Recent studies have demonstrated that genetic alterations may accompany acquisition of the angiogenic phenotype. Here we demonstrate that the recombinant adenovirus-mediated transfer of the wild-type p53 gene into a mutant p53-expressing human non-small cell lung cancer cell line markedly inhibited the expression of an angiogenic factor, vascular endothelial growth factor (VEGF), and increased the expression of a novel antiangiogenic factor, brain-specific angiogenesis inhibitor 1 (BAI 1), resulting in reduced neovascularization in vivo. These results may explain in part the mechanism of the bystander effect induced by wild-type p53 gene transfer of adjacent tumor cells.
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PMID:[Recombinant adenovirus expressing wild-type p53 is antiagiogenic--implication for lung cancer gene therapy]. 1094 20

The brain-specific angiogenesis inhibitor 1 gene has been isolated in an attempt to find fragments with p53 "functional" binding sites. As reported herein and by others, brain-specific angiogenesis inhibitor 1 expression is present in some normal tissues, but is reduced or lost in tumour tissues. Such data and its particular structure prompted the hypothesis that brain-specific angiogenesis inhibitor 1 may act as a mediator in the local angiogenesis balance. We herein demonstrate that brain-specific angiogenesis inhibitor 1 over-expression suppresses tumour angiogenesis, delaying significantly the human tumour growth in immunodeficient mice. The inhibitory effect of brain-specific angiogenesis inhibitor 1 was documented using our intravital microscopy system, strongly implicating brain-specific angiogenesis inhibitor 1 as a mediator in the control of tumour angiogenesis. In contrast, in vitro tumour cell proliferation was not inhibited by brain-specific angiogenesis inhibitor 1 transfection, whereas some level of cytotoxicity was assessed for endothelial cells. Immunohistochemical analysis of tumour samples confirmed a reduction in the microvessel density index in brain-specific angiogenesis inhibitor 1-overexpressing tumours. At messenger level, moderate changes could be detected, involving the down-regulation of vascular endothelial growth factor and collagenase-1 expression. Furthermore, brain-specific angiogenesis inhibitor 1 expression that was lost in a selection of human cancer cell lines could be restored by wild-type p53 adenoviral transfection. Brain-specific angiogenesis inhibitor 1 should be considered for gene therapy and development of efficient drugs based on endogenous antiangiogenic molecules.
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PMID:Overexpression of the p53-inducible brain-specific angiogenesis inhibitor 1 suppresses efficiently tumour angiogenesis. 1187 20

Brain-specific angiogenesis inhibitor 1 (BAI1) is a p53-target gene specifically expressed in the brain. We examined the distribution of the endogenous BAI1 protein in normal human brain tissue using a polyclonal antibody against the extracellular region of BAI1. Immunohistochemical study demonstrated that BAI1 was expressed in neuronal cells of the cerebral cortex but not in astrocytes. BAI1 protein was localized in the cellular cytoplasm and membrane. It was predominantly localized in the cellular membrane when expressed in cultured cells by means of gene transfection. BAI1 protein may play an important role in neuronal functions such as synapse formation and signal transduction.
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PMID:Brain-specific angiogenesis inhibitor 1 (BAI1) is expressed in human cerebral neuronal cells. 1207 42


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