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)

Electrophoretic immunoblotting (EIB [Western blotting]) has emerged as the major method for verification of seropositivity for human immunodeficiency virus (HIV) and therefore needs to be thoroughly characterized. The specificities of three EIB systems, our own and two commercial systems, were studied with anticellular sera and serial dilutions of human sera. We demonstrated that in one system, anti-HLA classes I and II gave bands comigrating with viral proteins, which can be controlled by EIB with uninfected H9 cells. In addition, animal antisera, including anti-immunoglobulin enzyme conjugates, occasionally reacted with HIV gag proteins, necessitating appropriate controls. Whereas none of 10 blood donors reacted at the standard dilution in serum (1/100 or 1/400) in any of the three systems, 6, 1, and 2 of 10 donors reacted with p24, p55, or both at a dilution of 1/10 for the three systems tested. Thus, nonspecific reactions can arise in several ways and justify critical EIB interpretation. The sensitivity of the three systems was studied by comparative titrations and direct quantification of bound immunoglobulin G (IgG). In the titrations with all three, the minor anti-HIV bands p53 and p64, coded from pol, were often detectable in higher dilutions than were antibodies to any other HIV protein. The minimum visible amounts of IgG bound per HIV protein band estimated by extra- and interpolation in densitometric curves and liquid scintillation counting of radiolabeled patient IgG were approximately 0.1, 0.05, and 0.02 ng per band in the three systems. One of the commercial systems had both the highest sensitivity and highest specificity.
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PMID:Specificities and sensitivities of three systems for determination of antibodies to human immunodeficiency virus by electrophoretic immunoblotting. 342 44

Active, recombinant p68 reverse transcriptase (RT) from human immunodeficiency virus type 2 (HIV-2), with an NH2-terminal extension containing a hexahistidine sequence was isolated from extracts of Escherichia coli by immobilized metal affinity chromatography. Treatment of the purified p68/p68 homodimer of HIV-2 RT with recombinant HIV-2 protease generates stable, active heterodimer (p68/p58) that is resistant to further hydrolysis. Analysis of this p68/p58 HIV-2 RT heterodimer revealed that while one subunit is intact p68, the p58 subunit is COOH-terminally truncated by cleavage, not at Phe440 as is seen in processing of the p66/p66 HIV-1 RT homodimer by HIV-1 protease, but at Met484. The expected COOH-terminal p10 fragment resulting from hydrolysis of p68 at Met484 is not released intact, but undergoes further cleavage at Asn494, Met503, and Tyr532. Processing of p68/p68 HIV-2 RT with the HIV-1 protease led to cleavage of the Phe440-Tyr441 bond, exactly as is seen with p66/p66 HIV-1 RT, to give the analogous p53 subunit. Studies of a peptide substrate modeled after residues 437-444 in HIV-2 RT showed that while the HIV-1 protease was able to cleave the Phe440 bond, this bond was resistant to cleavage by the HIV-2 enzyme. Our findings provide a rationale for the previous observation that the RT heterodimer isolated from HIV-2 lysates is larger than that from HIV-1. We conclude that the p68/p58 HIV-2 RT heterodimer, containing the Met484 truncated p58 subunit, is a biologically relevant form of the enzyme in vivo.
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PMID:The differential processing of homodimers of reverse transcriptases from human immunodeficiency viruses type 1 and 2 is a consequence of the distinct specificities of the viral proteases. 753 31

The purpose of this study was to characterize the clinical and histological features of intraoral squamous cell carcinoma in men who were seropositive for the human immunodeficiency virus and to evaluate viral cofactors (human papillomavirus, herpes simplex virus, Epstein-Barr virus), proliferative index (proliferating cell nuclear antigen), a factor associated with invasion (cathepsin D), and mutated tumor suppressor gene and proto-oncogene products (mutated p53, c-erbB-2). Four men who were seropositive for the human immunodeficiency virus and had acquired immunodeficiency syndrome presented with painful oral lesions of variable duration. Oral cancer risk factors included heavy tobacco use (four of four), heavy alcohol use (three of four), and previous radiotherapy (one of four). The lesions consisted of ulcers (two of four), a fungating mass (one of four), and papillary erythroplakia (one of four). Incisional biopsy specimens were obtained. High-stringency in situ hybridization was performed with DNA probes to the human papillomavirus (types 6/11; 16/18; 31/33/35) and Epstein-Barr virus: Immunocytochemical studies for the herpes simplex virus, proliferating cell nuclear antigen, cathepsin D, mutated p53, and c-erbB-2 were performed. Two lesions were moderately differentiated squamous cell carcinoma, one lesion was a basaloid squamous cell carcinoma, and one was carcinoma in situ. Stage of disease at diagnosis was II (one of four), III (two of four), and IV (one of four). Three cases were positive for the human papillomavirus, one case was positive for Epstein-Barr virus, and three cases were positive for the herpes simplex virus. C-erbB-2 was focally positive in one case, and mutated p53 was positive in a separate case.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Intraoral squamous cell carcinoma in human immunodeficiency virus infection. A clinicopathologic study. 755 63

The skin-associated lymphoid tissue is composed of keratinocytes, Langerhans cells, skin trophic T cells, and lymphatic endothelial cells of the skin. The epidermis, which is involved in many viral infections, contains all of the components needed for an effective immune response: antigen-presenting Langerhans cells, T cells, and cytokines from leukocytes and keratinocytes. There have been some recent advances in the study of the cutaneous immunology involved in infections with the human immunodeficiency virus (HIV), human papillomavirus (HPV), and herpes simplex virus (HSV). In general, viral diseases with cutaneous manifestations lead to a decline in epidermal Langerhans cell numbers, which probably reflects Langerhans cell emigration out of the epidermis and entry into regional lymph nodes, leading to Langerhans cell activation and antigen presentation to T cells. In HSV, there is a subsequent T-cell infiltration of the epidermis, composed of CD4+ cells that have both immune modulatory action and direct cytotoxic action. In HIV, where there is a systemic depletion of CD4+ cells, the epidermis is left with reduced numbers of T cells. Intradermal injection of interleukin-2, however, leads to an epidermal cellular infiltration in HIV+ individuals. In HPV-induced condyloma, intralesional interferon increases Langerhans cells and CD4+ and CD8+ cells in the skin, as well as transforming growth factor beta 1, tumor necrosis factor-alpha, pRB, and p53. Therefore, viral infections involving the epidermal immune system have certain similar characteristics, whereas other factors are unique to the infecting virus.
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PMID:Skin-associated lymphoid tissue in human immunodeficiency virus-1, human papillomavirus, and herpes simplex virus infections. 761 7

Tumor necrosis factor alpha (TNF) is a potent activator of transcription directed by the human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR). We have recently reported that the p53 tumor suppressor gene product binds to a site within the Sp1 binding region of the HIV-1 LTR and contributes to the TNF induction of this promoter. In this study we show that the transcription factor Sp1 cooperates with p53 in the transcriptional activation directed by the HIV-1 LTR. The presence of Sp1 increased p53 binding to its recognition sequence in the HIV-1 LTR, and experiments in Drosophila cells show that Sp1 is necessary for full transactivation by mutant p53. Importantly, TNF induced the association between p53 and Sp1 in Jurkat T cells. These data demonstrate a synergistic role for these proteins in the mechanism of TNF induction of HIV-1 LTR-mediated transcription and suggest that Sp1 may play an important role in modulating certain functions of p53.
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PMID:p53 and Sp1 interact and cooperate in the tumor necrosis factor-induced transcriptional activation of the HIV-1 long terminal repeat. 764 77

Adenosine deaminase (ADA, EC 3.5.4.4) is a ubiquitous enzyme in the purine catabolic pathway. In contrast to the widespread tissue distribution of this enzyme, inherited ADA deficiency in human results in a tissue-specific severe combined immunodeficiency. To explain the molecular basis for this remarkable tissue specificity, we have used a genetic approach to study ADA deficiency. We demonstrate that ADA deficiency causes depletion of CD8low transitional and CD4+CD8+ double-positive thymocytes by an apoptotic mechanism. This effect is mediated by a p53-dependent pathway, since p53-deficient mice are resistant to the apoptosis induced by ADA deficiency. DNA damage, known to be caused by the abnormal accumulation of dATP in ADA deficiency, is therefore responsible for the ablation of T-cell development and for the immunodeficiency. The two thymocyte subsets most susceptible to apoptosis induced by ADA deficiency are also the two thymocyte subsets with the lowest levels of bcl-2 expression. We show that thymocytes from transgenic mice that overexpress bcl-2 in the thymus are rescued from apoptosis induced by ADA deficiency. Thus, the tissue specificity of the pathological effects of ADA deficiency is due to the low bcl-2 expression in CD8low transitional and CD4+CD8+ double-positive thymocytes.
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PMID:p53 expression is required for thymocyte apoptosis induced by adenosine deaminase deficiency. 766 98

Transforming mutants of the p53 tumor suppressor gene can positively regulate transcription from several promoters that do not contain known p53 binding sites. Here, we report the identification of a novel p53 binding site in the human immunodeficiency virus long terminal repeat that specifically mediates mutant p53 transactivation. This DNA element was bound by endogenous Jurkat p53 when these cells were stimulated by tumor necrosis factor. Mutation of this sequence inhibited p53 transactivation and tumor necrosis factor inducibility of the human immunodeficiency virus type 1 long terminal repeat. In addition, this DNA element was found to be sufficient to confer mutant p53 responsiveness on a heterologous minimal promoter. It has been hypothesized that transforming mutants of p53 represent a proliferative conformational stage that can be adopted by the native protein under stimulation by growth factors. The data presented suggest that proliferative and antiproliferative p53 conformations recognize different DNA binding sites in order to mediate distinct biological functions. Thus, transforming mutants of p53 that fold into the proliferative conformation would favor proliferative over antiproliferative functions.
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PMID:A proliferative p53-responsive element mediates tumor necrosis factor alpha induction of the human immunodeficiency virus type 1 long terminal repeat. 776 Aug 42

Infection by human immunodeficiency virus type 1 (HIV-1) causes acquired immunodeficiency syndrome (AIDS) after a long clinical latency. This disease is associated with a spectrum of cancers. Here we report that wild-type p53 is a potent suppressor of Tat, a major transactivator of HIV-1. Reciprocally, Tat inhibits the transcription of p53. Downregulation of p53 by upregulated tat may be important for the establishment of productive viral infection in a cell and also may be involved in the development of AIDS-related malignancies.
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PMID:Reciprocal modulations between p53 and Tat of human immunodeficiency virus type 1. 777 31

Lymphoma is one of the defining manifestations of AIDS. Most of these lymphoproliferations are high-grade B-cell non-Hodgkin's lymphoma. Unlike lymphoproliferations that arise in other settings of immunodeficiency, HIV-related lymphomas have a variable association with Epstein-Barr virus (EBV) and also contain alterations in c-myc and p53. EBV infection appears to precede clonal expansion, and its latent expression pattern (Epstein-Barr nuclear antigen1+/Epstein Barr nuclear antigen 2-/latent membrane protein+) is unique among non-Hodgkin's lymphomas. Both EBV types A and B are present in HIV-related lymphomas. Mutations in c-myc include translocations and point mutations. Other altered loci include ras and bcl-6. Although all of these somatic alterations can be detected in lymphomas arising in the general population, their accumulation in a relatively short period (6 to 8 years) after HIV infection suggests an acceleration of underlying mechanisms.
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PMID:Biologic aspects of AIDS-related lymphoma. 782 54

Ataxia-telangiectasia is a progressive recessive disease featuring neurodegeneration, immunodeficiency, chromosomal instability, radiation hypersensitivity and increased predisposition to cancer. Impaired induction of the tumor suppressor protein p53 after gamma-irradiation was recently reported. All together these characteristics may be compatible with an inability to correctly regulate the apoptotic pathway of cell death in this syndrome. We show here that lymphocyte cultures from AT patients are characterized by a 3 times more elevated spontaneous level of apoptotic cells compared to normal ones. In spite of this, 24 h after exposure to gamma-irradiation (5 to 10 Gy), AT lymphocytes show a dramatically reduced capacity to undergo apoptosis compared to normal cells. We obtained similar results on EBV-transformed lymphoblasts. Interestingly, lymphoblasts from obligate heterozygous for the AT mutation(s) show the same features as AT lymphoblasts, i.e. an elevated frequency of spontaneous and a reduced level of radio-induced apoptotic figures in comparison to normal cultured cells. In conclusion, we show here, for the first time, that mutation(s) in AT gene(s) results in an impaired ability to correctly regulate the apoptotic pathway of cell death.
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PMID:[Changes in the radiation-induced apoptotic response in homozygotes and heterozygotes for the ataxia-telangiectasia gene]. 788 43


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