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)

There are abnormalities in the structure and/or function of several oncogenes and growth factors in human pancreatic cancer, notably the EGF receptor and its ligand TGF alpha, c-erb B-2 proto-oncogene, Ki-ras oncogene and the tumour suppressor gene p53. The temporal sequence of their activation and the nature of the aetiological agents responsible for their activation are not yet clear. In vitro pancreatic culture systems and transgenic animal experiments are needed to reconstruct and define those molecular events that are necessary and sufficient for the neoplastic phenotype.
Baillieres Clin Gastroenterol 1990 Dec
PMID:Growth factors and oncogenes in pancreatic cancer. 196 2

We have studied the role of a previously described tubulovesicular compartment near the cis-Golgi apparatus in endoplasmic reticulum (ER)-to-Golgi protein transport by light and immunoelectron microscopy in Vero cells. The compartment is defined by a 53-kDa transmembrane protein designated p53. When transport of the vesicular stomatitis virus strain ts045 G protein was arrested at 39.5 degrees C, the G protein accumulated in the ER but had access to the p53 compartment. At 15 degrees C, the G protein was exported from the ER into the p53 compartment which formed a compact structure composed of vesicular and tubular profiles in close proximity to the Golgi. Upon raising the temperature to 32 degrees C, the G protein migrated through the Golgi apparatus while the p53 compartment resumed its normal structure again. These results establish the p53 compartment as the 15 degrees C intermediate of the ER-to-Golgi protein transport pathway.
Eur J Cell Biol 1990 Dec
PMID:Identification of an intermediate compartment involved in protein transport from endoplasmic reticulum to Golgi apparatus. 196 13

The large T-antigens of SV40 and polyoma virus are nuclear, multifunctional proteins that are essential for replication of the respective viruses. They can also 'transform' cells in culture to varying extents; both can immortalise primary cells, and SV40 large T can additionally induce full transformation. Recently, p105Rb, the protein product of the anti-oncogene RB-1, has been shown to interact with both large T-antigens. SV40 large T-antigen also binds to a p105Rb related protein, p107. SV40 large T differs from that of polyoma virus in its ability to associate with another anti-oncogene product, p53. The significance of these properties to the transforming potential of both viruses is considered.
Semin Cancer Biol 1990 Dec
PMID:Cell alterations induced by the large T-antigens of SV40 and polyoma virus. 196 92

Human papillomaviruses (HPVs) appear to play a role in the etiology of the vast majority of virus-associated human malignancies. Studies of viral gene expression in carcinomas suggest the importance of two HPV encoded proteins, E6 and E7, in malignant development and these proteins have been shown to encode transforming and immortalising activities. The two proteins show some functional resemblance to the transforming proteins of other small DNA tumour viruses such as adenovirus and SV40. Recent evidence suggests that one important function of these virus-encoded proteins is binding the products of the cellular tumour suppressor genes RB and p53, revealing an exciting link between oncogenes and anti-oncogenes.
Semin Cancer Biol 1990 Dec
PMID:Human papillomavirus oncoproteins. 196 93

Oncogenic transformation by the human adenoviruses involves the concerted action of two genes, E1A and E1B. Over the last few years the products of these genes have been characterised in considerable detail using genetic, immunological and biochemical means. The E1A gene by itself can immortalise primary cells and can cooperate to effect full morphological transformation not only with E1B but also with other known oncogenes. The immortalisation and cooperation activities of E1A require multiple functions that are directed by structurally and functionally independent regions of the E1A protein. These regions coincide with sites of protein: protein interaction between E1A and a variety of cellular polypeptides. One of these, the Rb protein, is a known regulator of the mammalian cell cycle. The E1B region encodes two proteins required for transformation, the larger of which binds to the p53 cellular protein. This protein has also been implicated as a negative regulator of cell growth. It appears therefore that E1A and E1B carry out their many functions associated with transformation at least in part by binding to and presumably modulating the activity of key cellular regulators.
Semin Cancer Biol 1990 Dec
PMID:Transformation by the human adenoviruses. 210 12

The 55K protein encoded by the adenovirus 2 E1B gene is required for complete cellular transformation and binds the cellular protein p53. Using an in vitro immunoprecipitation assay, we mapped the domains in both 55K and p53 required for the interaction of the two proteins. The domain in p53 mapped to the amino terminal 123 residues. There are several domains in the 495 residue 55K polypeptide which contribute to stable association with p53, with the most essential region mapping between residues 224 and 354. Mutations which prevented 55K-p53 binding were not more defective for transformation than other mutations which did not affect binding.
Virology 1990 Dec
PMID:Domains required for in vitro association between the cellular p53 and the adenovirus 2 E1B 55K proteins. 214 4

A novel class of oncogene has been recognised whose loss-of-function results in the expression of the malignant phenotype. Two examples of such genes are the human retinoblastoma predisposition gene (RB1) and the gene encoding the cellular protein p53. These genes are thought to regulate and limit normal proliferation of cells and, as a consequence, can suppress tumorigenicity when introduced into transformed cells. They are hence frequently described as 'tumour suppressor genes'. Both RB1 and p53 gene products are bound by various transforming early proteins encoded by the DNA tumour viruses SV40, adenovirus and human papilloma virus. It is thought that they are thus sequestered and rendered inactive. Thus, a coherent model is emerging whereby inactivation, either by mutation of sequestration, of these tumour suppressor genes may contribute to natural and experimental carcinogenic processes.
Semin Cancer Biol 1990 Dec
PMID:The nuclear oncoproteins: RB and p53. 215 36

Murine p53 blocks many of the replication activities of simian virus 40 (SV40) large tumor antigen (T antigen) in vitro. As murine cells do not replicate SV40 DNA, it was of interest to determine how p53 from permissive human cells functions. Recombinant baculoviruses encoding either the wild-type form of human p53 or a mutant p53 cloned from a human tumor cell line were constructed, and p53 proteins were purified from infected insect cells. Surprisingly, we found that wild-type human p53 was as inhibitory to the ability of T antigen to mediate replication of an SV40 origin-containing (ori DNA) plasmid in vitro as was murine p53. Wild-type human p53 also blocked the DNA unwinding activity of T antigen, as did its murine counterpart. In contrast to murine and wild-type human p53, the mutant human p53 did not block ori DNA replication or DNA unwinding. Murine p53 formed a complex with mutant human p53 in vivo. Furthermore, mutant human p53 reduced the inhibition of SV40 ori DNA replication by murine p53 in vitro. These results provide a model for the way in which mutant p53 proteins can affect normal functions of p53.
Proc Natl Acad Sci U S A 1990 Dec
PMID:Wild-type, but not mutant, human p53 proteins inhibit the replication activities of simian virus 40 large tumor antigen. 217 57

The development of human lung cancer may require multiple genetic deletions affecting a number of chromosomes, e.g., 1, 3, 11, 13, and 17. These genetic aberrations may induce the activation of proto-oncogenes (c-jun, ras, c-raf1) and the loss of tumor suppressor genes (p53). Some of the activated proto-oncogenes and tumor suppressor genes are more selectively expressed or absent in small-cell lung cancer (L-myc, c-myb, c-scr, Rb gene) or non-small-cell lung cancer (c-erbB-2, c-sis, c-fes). These genes may thus be of importance for selection of differentiation pathway. The c-myc oncogene is frequently amplified in small-cell lung cancer cell lines in a much higher frequency than in vivo. This indicates that c-myc seems to be related to tumor progression and a relatively late event in the lung cancer development. The uncontrolled production of multiple growth factors has been identified in human lung cancer cell lines. These factors can promote and inhibit the proliferation via paracrine and autocrine loops via specific receptors. The products from some of the activated proto-oncogenes (c-sis, c-erbB-2) are sequences homologous to a certain growth factor (PDGF) and a receptor (EGF) identified in lung cancer. The production and action of these growth factors may be of major importance for further activation of proto-oncogenes via intracellular signal transduction and specific oncogenic activation leading to further tumor progression.
Am Rev Respir Dis 1990 Dec
PMID:Gene amplification in human lung cancer. The myc family genes and other proto-oncogenes and growth factor genes. 217 59

The p53 gene is functionally inactivated mostly by point mutations resulting in amino acid substitutions in a wide variety of human cancers. We found a novel mutation of the p53 gene in a small cell lung carcinoma cell line, Lu-143. One of the allelic p53 genes was lost accompanied by loss of heterozygosity for chromosome 17. In the remaining allelic p53 gene, there was a single-base substitution of G to T at position 1 within the splice donor site of intron 7, and the mutated intron was not spliced out during the mRNA maturation process. As a result of this mutation, larger sized p53 mRNA was expressed and no p53 specific protein was detected in this cell line. These results suggest that mutations causing splicing abnormalities are one of the molecular mechanisms for the p53 gene inactivation in human cancer.
Biochem Biophys Res Commun 1990 Dec 14
PMID:Point mutation of the p53 gene resulting in splicing inhibition in small cell lung carcinoma. 217 5


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