Disease relevance of POLE3

• The human immunodeficiency virus (HIV) matrix protein, p17, forms the outer shell of the core of the virus, lining the inner surface of the viral membrane [1].
• Structural similarity between the p17 matrix protein of HIV-1 and interferon-gamma [1].
• Electron microscopy of cryosections showed virus particles, identified by their morphology and positive labeling with antibodies to the viral p17, p24, and envelope proteins, in intracellular vacuoles [2].
• The recombinant 26-kDa precursor undergoes rapid self-processing both in E. coli and in vitro at the NH2 terminus, yielding a proteolytically active 17-kDa protein, p17 [3].
• Decline in IgG antibody reactivity to HIV core protein p17 appears to be an earlier marker of disease progression than the previously reported decline in anti-p24 reactivity, and may be of value in selecting individuals for secondary prevention of HIV-related disease development [4].

High impact information on POLE3

• The antiviral activity of the antiserum was found to be due to a region of homology between thymosin alpha 1 and p17, a product of the gag gene of HTLV-III/LAV [5].
• We further provide evidence that p17 is synthesized by N-terminal proteolytic processing of p25 by a serine protease [6].
• Antigenic variation was also detected in the p17 Gag epitope; a dominant viral variant present in the patient was well recognized by a specific CD4(+) T lymphocyte line, whereas several natural mutants were not [7].
• 12 (28%) showed a positive response, and we went on to map dominant epitopes in two individuals, to p24 Gag restricted by human histocompatibility leukocyte antigen (HLA)-DR1 and to p17 Gag restricted by HLA-DRB52c [7].
• Subcutaneous injection of p17 (a peptide consisting of 17 NH2-terminal aminoacids of MBP) in complete Freund's adjuvant (CFA) causes paralysis [8].

Chemical compound and disease context of POLE3

• Both avarone and avarol block in a dose-dependent manner the expression of the p24 and p17 gag proteins of HTLV-III in H9 cells after virus infection and block viral replication, as judged by approximately 80% inhibition of reverse transcriptase activity [9].
• Together, these data are consistent with a model of polarized virus budding in which capsid proteins, lacking a targeting signal, are targeted for specific basolateral release via an interaction of p17 with the envelope glycoprotein containing the polarization signal in its intracytoplasmic domain [10].
• Env C2/V3, gag p17/p24, pol protease, and RT regions of HIV-1 isolates recently obtained from 25 HIV-1 seropositive individuals from Ho Chi Minh City (Vietnam) were studied, and genes subtypes were determined by DNA sequence analyses [11].
• Serial sections of formol-fixed and paraffin-embedded CNS tissues from 70 patients (69 with acquired immune deficiency syndrome, AIDS) were immunolabeled with monoclonal antibodies against HIV antigens (Ags) p17, p24, and gp41 [12].
• We assessed the induction of these cytokines in PMC from HIV-infected (HIV+) and uninfected (control) gravidae following exposure to lipopolysaccharide (LPS), HIV lysate (iHIV), recombinant HIV env (GP160) and HIV gag (gag55), and synthetic HIV p17 (HGP30) antigens [13].

Biological context of POLE3

• The genes for p17 and p12 can be assigned to chromosome locations 9q33 and 2p12, respectively [14].
• The antioxidants N-acetylcysteine and the combination of vitamins C and E prevented oxLDL-induced apoptosis, abrogated the enhancement of CPP32-like protease activity, and inhibited the proteolytic cleavage of CPP32 into its active subunit p17 [15].
• The p17 gag and env V3 regions of the HIV-1 genome were directly sequenced from uncultured lymphocytes [16].
• Two amino acid sequences, ESMD downward arrowS (amino acids 25-29) and IETD downward arrowS (amino acids 172-176), in the precursor have been defined as the cleavage sites for the production of the p17 and p12 subunits [17].
• These results suggest that a "myristoyl-protein switch" regulates the reversible membrane targeting of p17 by protein kinase C-mediated phosphorylation [18].

Anatomical context of POLE3

• HIV gag-specific CTL precursors are identified at frequencies of 1/1700 to 1/17,000 lymphocytes and are made up of cells with both p17 and p24 specificities [19].
• Limiting dilution analysis of cytotoxic T lymphocytes to human immunodeficiency virus gag antigens in infected persons: in vitro quantitation of effector cell populations with p17 and p24 specificities [19].
• The selection of HGP-30 as the p17 peptide to be evaluated in early studies is based on the presence of both T-cell and B-cell epitopes as predicted by computer modeling and mouse studies and the demonstration of in vitro neutralization activity by antibodies to the epitope [20].
• This modification, introduced to enhance interaction of the polyanions with cell membranes, significantly increases the antiviral activity of the oligomers, as judged by inhibition of syncytia formation and expression of viral proteins p17, p24, and reverse transcriptase for human immunodeficiency virus 1 in Molt-3 cells [21].
• In addition, the proteolytic cleavage of CPP32 resulting in the formation of two active fragments (p17 and p12) was observed in cytosolic extracts from TPEN-treated Jurkat cells, but not in extracts which were prepared from cells treated with TPEN in the presence of VADcmk or DEVD-CHO [22].

Associations of POLE3 with chemical compounds

• Proteins p17 and p18 are closely related to each other, with 48% identical residues and carboxyl tails containing almost exclusively lysine, alanine, and serine or threonine residues [23].
• Whereas all S-nitroso bonds in the p12 subunit were cleaved with release of NO and partial formation of protein-mixed disulfides with glutathione, a single S-nitrosation in the p17 subunit remained stable [24].
• Greater than 98% of the total recovered p17 was myristylated at the N-terminal glycine residue, and the measured molecular weights (as determined by electrospray ionization mass spectrometry) of the most abundant forms were within 3 atomic mass units of the calculated molecular weights (15,266) [25].
• Using transient transfection of a human liver cell line with constructs expressing wild-type p17 or a series of Cys mutants of p17, we show that Cys-7 forms an intramolecular S-S bond to Cys61, which in assembly-competent core proteins is available for intermolecular disulfide bonds between two neighboring subunits [26].
• Lactacystin treatment decreased the p32 zymogen and evoked the accumulation of the p17 and p12 subunits [27].

Analytical, diagnostic and therapeutic context of POLE3

• In addition, ongoing paralysis is ameliorated by subsequent intraperitoneal injection of p17 in IFA [8].
• Analysis of caspase 3 protein expression by Western blot analysis revealed that 4-HPR resulted in a significant increase in the appearance of the active p17 subunit without effecting a concomitant change in p32 procaspase 3 levels [28].
• Epitope mapping studies revealed the presence of HLA class I-restricted CTL responses to six different epitopes in p17, p24, RT, Env, and Nef, which conferred broadly cross-reactive recognition of reported HIV-1 variants [29].
• We separated p17 and p18 by SDS-PAGE and obtained N-terminal amino acid sequence to identify these phosphorproteins as histones H2b and H3, respectively [30].
• Systematic screening of blood donations by enzyme-linked immunosorbent assay (ELISA) for HIV antibodies carries a false-positive rate: the sera involved react in Western blot to core antigens (p24 or p17) but reactivity to envelope is absent [31].

References