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

Sève, Michel; Favier, Alain; Osman, Mohamed; Hernández, Daniel; Vaitaitis, Gisela M.; Flores, Natalia C.; McCord, Joe M.; Flores, Sonia C.

doi:10.1006/abbi.1998.0942

Cited by 56 publications

(30 citation statements)

References 48 publications

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“…Along the same lines, HIV-1 Tat has been shown to bind to p53 (9,26,27) and is proposed to be important for the development of HIV-1-related malignancies (26). Interestingly, Tat expression has also been related to increased apoptosis in infected cells (40,46). We therefore wished to exam-…”

Section: Resultsmentioning

confidence: 99%

Loss of G ₁ /S Checkpoint in Human Immunodeficiency Virus Type 1-Infected Cells Is Associated with a Lack of Cyclin-Dependent Kinase Inhibitor p21/Waf1

Clark¹,

Santiago²,

Deng³

et al. 2000

J Virol

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Productive high-titer infection by human immunodeficiency virus type 1 (HIV-1) requires the activation of target cells. Infection of quiescent peripheral CD4 lymphocytes by HIV-1 results in incomplete, labile reverse transcripts and lack of viral progeny formation. An interplay between Tat and p53 has previously been reported, where Tat inhibited the transcription of the p53 gene, which may aid in the development of AIDS-related malignancies, and p53 expression inhibited HIV-1 long terminal repeat transcription. Here, by using a well-defined and -characterized stress signal, gamma irradiation, we find that upon gamma irradiation, HIV-1-infected cells lose their G 1 /S checkpoints, enter the S phase inappropriately, and eventually apoptose. The loss of the G 1 /S checkpoint is associated with a loss of p21/Waf1 protein and increased activity of a major G 1 /S kinase, namely, cyclin E/cdk2. The p21/Waf1 protein, a known cyclin-dependent kinase inhibitor, interacts with the cdk2/cyclin E complex and inhibits progression of cells into S phase. We find that loss of the G 1 /S checkpoint in HIV-1-infected cells may in part be due to Tat's ability to bind p53 (a known activator of the p21/Waf1 promoter) and sequester its transactivation activity, as seen in both in vivo and in vitro transcription assays. The loss of p21/Waf1 in HIV-1-infected cells was specific to p21/Waf1 and did not occur with other KIP family members, such as p27 (KIP1) and p57 (KIP2). Finally, the advantage of a loss of the G 1 /S checkpoint for HIV-1 per se may be that it pushes the host cell into the S phase, which may then allow subsequent virus-associated processes, such as RNA splicing, transport, translation, and packaging of virion-specific genes, to occur.

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Section: Resultsmentioning

confidence: 99%

Loss of G ₁ /S Checkpoint in Human Immunodeficiency Virus Type 1-Infected Cells Is Associated with a Lack of Cyclin-Dependent Kinase Inhibitor p21/Waf1

Clark¹,

Santiago²,

Deng³

et al. 2000

J Virol

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“…It was already shown that restoring antioxidant capacity paralleled immunologic and virologic improvements (53-55). The HIV Tat protein was able to suppress antioxidant factor expression (56,57). Ongoing oxidative stress resulting from HIV infection stimulated Fas-induced CD4 ϩ T-lymphocyte apoptosis and mediated a Tat-and gp160-induced functional impairment of uninfected T-lymphocytes and enhanced NF-B-dependent activation of virus transcription (56, 58 -60).…”

Section: Inhibition Of Hiv-1 Replication Through Nkef-a and Nkef-b Trmentioning

confidence: 99%

HIV-1 Antiviral Activity of Recombinant Natural Killer Cell Enhancing Factors, NKEF-A and NKEF-B, Members of the Peroxiredoxin Family

Geiben-Lynn¹,

Kursar²,

Brown³

et al. 2003

Journal of Biological Chemistry

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CD8؉ T-cells are a major source for the production of non-cytolytic factors that inhibit HIV-1 replication. In order to characterize further these factors, we analyzed gene expression profiles of activated CD8؉ T-cells using a human cDNA expression array containing 588 human cDNAs. mRNA for the chemokine I-309 (CCL1), the cytokines granulocyte-macrophage colony-stimulating factor and interleukin-13, and natural killer cell enhancing factors (

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“…One of the viral proteins that strongly affect neuronal survival and function is Tat, which is expressed at an early stage of viral infection and plays a pivotal role in transcriptional activation of HIV-1-LTR (Gaynor, 1995). By interacting with different host proteins, Tat has been shown to promote survival and proliferation in various cell types (Ensoli et al, 1993;Zauli et al, 1993Zauli et al, , 1995Lotz et al, 1994;Seve et al, 1999;Cantaluppi et al, 2001), and in some cases promote apoptosis (Nath et al, 1996;Kruman et al, 1998). There is a growing line of evidence supporting the functional crosstalk between nerve growth factor (NGF) action and HIV-1 infection.…”

Section: Introductionmentioning

confidence: 99%

HIV-Tat promotes cellular proliferation and inhibits NGF-induced differentiation through mechanisms involving Id1 regulation

et al. 2004

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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

Cited by 56 publications

References 48 publications

Loss of G ₁ /S Checkpoint in Human Immunodeficiency Virus Type 1-Infected Cells Is Associated with a Lack of Cyclin-Dependent Kinase Inhibitor p21/Waf1

Loss of G ₁ /S Checkpoint in Human Immunodeficiency Virus Type 1-Infected Cells Is Associated with a Lack of Cyclin-Dependent Kinase Inhibitor p21/Waf1

HIV-1 Antiviral Activity of Recombinant Natural Killer Cell Enhancing Factors, NKEF-A and NKEF-B, Members of the Peroxiredoxin Family

HIV-Tat promotes cellular proliferation and inhibits NGF-induced differentiation through mechanisms involving Id1 regulation

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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

Cited by 56 publications

References 48 publications

Loss of G 1 /S Checkpoint in Human Immunodeficiency Virus Type 1-Infected Cells Is Associated with a Lack of Cyclin-Dependent Kinase Inhibitor p21/Waf1

Loss of G 1 /S Checkpoint in Human Immunodeficiency Virus Type 1-Infected Cells Is Associated with a Lack of Cyclin-Dependent Kinase Inhibitor p21/Waf1

HIV-1 Antiviral Activity of Recombinant Natural Killer Cell Enhancing Factors, NKEF-A and NKEF-B, Members of the Peroxiredoxin Family

HIV-Tat promotes cellular proliferation and inhibits NGF-induced differentiation through mechanisms involving Id1 regulation

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Product

Resources

About

Loss of G ₁ /S Checkpoint in Human Immunodeficiency Virus Type 1-Infected Cells Is Associated with a Lack of Cyclin-Dependent Kinase Inhibitor p21/Waf1

Loss of G ₁ /S Checkpoint in Human Immunodeficiency Virus Type 1-Infected Cells Is Associated with a Lack of Cyclin-Dependent Kinase Inhibitor p21/Waf1