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The human immunodeficiency virus-1 Tat protein increases cell proliferation, alters sensitivity to zinc chelator-induced apoptosis, and changes Sp1 DNA binding in HeLa cells.
Arch Biochem Biophys 1999; 361(2):165-72AB

Abstract

The HIV-1 transcriptional regulatory protein Tat is a pleiotropic factor that represses expression of the human Mn-superoxide dismutase. Tat increases oxidative stress, as shown by decreased glutathione and NADPH levels. These redox changes enhance proliferation and apoptosis and alter the activity of zinc thiolate-containing proteins such as Sp1. Cells stably producing the Tat protein have an increased proliferation rate, which can be inhibited by pretreatment with the antioxidant mercaptopropionylglycine. Conversely, cells exposed to low concentrations of the oxidant paraquat are stimulated to divide. Intermediate and higher paraquat levels result in increased apoptosis or necrosis, respectively, suggesting that the physiological end point depends on the dose of oxidant used. Furthermore, treatment with the zinc chelator (N,N,N', N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) sensitizes HeLa-tat cells to apoptosis. In these cells, binding of the zinc-containing factor Sp1 to its DNA sequence is higher than in parental cells. Normal DNA binding is partially restored by pretreatment with a compound that mimics superoxide dismutase activity. Interestingly, Sp1-DNA interactions decrease more rapidly in the HeLa-tat cells after TPEN treatment. HeLa cell extracts incubated in the presence of purified Tat protein have increased Sp1 binding, consistent with the results observed in Tat-transfected cells. These results suggest that the Tat protein, via direct or indirect mechanisms, increases proliferation, sensitizes cells to apoptosis, and changes the conformation of Sp1, affecting its ability to bind to its cognate DNA sequence and to retain its zinc.

Authors+Show Affiliations

Laboratoire de Biologie du Stress Oxydant (LBSO), University of Grenoble, La Tronche, 38700, France. Michel.Seve@ujf-grenoble.frNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

9882443

Citation

Seve, M, et al. "The Human Immunodeficiency Virus-1 Tat Protein Increases Cell Proliferation, Alters Sensitivity to Zinc Chelator-induced Apoptosis, and Changes Sp1 DNA Binding in HeLa Cells." Archives of Biochemistry and Biophysics, vol. 361, no. 2, 1999, pp. 165-72.
Seve M, Favier A, Osman M, et al. The human immunodeficiency virus-1 Tat protein increases cell proliferation, alters sensitivity to zinc chelator-induced apoptosis, and changes Sp1 DNA binding in HeLa cells. Arch Biochem Biophys. 1999;361(2):165-72.
Seve, M., Favier, A., Osman, M., Hernandez, D., Vaitaitis, G., Flores, N. C., ... Flores, S. C. (1999). The human immunodeficiency virus-1 Tat protein increases cell proliferation, alters sensitivity to zinc chelator-induced apoptosis, and changes Sp1 DNA binding in HeLa cells. Archives of Biochemistry and Biophysics, 361(2), pp. 165-72.
Seve M, et al. The Human Immunodeficiency Virus-1 Tat Protein Increases Cell Proliferation, Alters Sensitivity to Zinc Chelator-induced Apoptosis, and Changes Sp1 DNA Binding in HeLa Cells. Arch Biochem Biophys. 1999 Jan 15;361(2):165-72. PubMed PMID: 9882443.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The human immunodeficiency virus-1 Tat protein increases cell proliferation, alters sensitivity to zinc chelator-induced apoptosis, and changes Sp1 DNA binding in HeLa cells. AU - Seve,M, AU - Favier,A, AU - Osman,M, AU - Hernandez,D, AU - Vaitaitis,G, AU - Flores,N C, AU - McCord,J M, AU - Flores,S C, PY - 1999/1/12/pubmed PY - 1999/1/12/medline PY - 1999/1/12/entrez SP - 165 EP - 72 JF - Archives of biochemistry and biophysics JO - Arch. Biochem. Biophys. VL - 361 IS - 2 N2 - The HIV-1 transcriptional regulatory protein Tat is a pleiotropic factor that represses expression of the human Mn-superoxide dismutase. Tat increases oxidative stress, as shown by decreased glutathione and NADPH levels. These redox changes enhance proliferation and apoptosis and alter the activity of zinc thiolate-containing proteins such as Sp1. Cells stably producing the Tat protein have an increased proliferation rate, which can be inhibited by pretreatment with the antioxidant mercaptopropionylglycine. Conversely, cells exposed to low concentrations of the oxidant paraquat are stimulated to divide. Intermediate and higher paraquat levels result in increased apoptosis or necrosis, respectively, suggesting that the physiological end point depends on the dose of oxidant used. Furthermore, treatment with the zinc chelator (N,N,N', N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) sensitizes HeLa-tat cells to apoptosis. In these cells, binding of the zinc-containing factor Sp1 to its DNA sequence is higher than in parental cells. Normal DNA binding is partially restored by pretreatment with a compound that mimics superoxide dismutase activity. Interestingly, Sp1-DNA interactions decrease more rapidly in the HeLa-tat cells after TPEN treatment. HeLa cell extracts incubated in the presence of purified Tat protein have increased Sp1 binding, consistent with the results observed in Tat-transfected cells. These results suggest that the Tat protein, via direct or indirect mechanisms, increases proliferation, sensitizes cells to apoptosis, and changes the conformation of Sp1, affecting its ability to bind to its cognate DNA sequence and to retain its zinc. SN - 0003-9861 UR - https://www.unboundmedicine.com/medline/citation/9882443/The_human_immunodeficiency_virus_1_Tat_protein_increases_cell_proliferation_alters_sensitivity_to_zinc_chelator_induced_apoptosis_and_changes_Sp1_DNA_binding_in_HeLa_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0003-9861(98)90942-0 DB - PRIME DP - Unbound Medicine ER -