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Epie, Nicolas; Ammosova, Tatyana; Sapir, Tamar; Voloshin, Yaroslav; Lane, William S.; Turner, W.; Reiner, Orly; Nekhai, Sergeï

doi:10.1186/1742-4690-2-6

Cited by 29 publications

(6 citation statements)

References 43 publications

(59 reference statements)

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“…This is demonstrated by the present findings with regard to Tat(1-86) effects on tubulin polymerization, as well as other preparations employing purified tubulin [16, 17] and evidence that Tat(1-72) co-immunoprecipitates with LIS-1 [20]. It has also been shown that exposure to Tat variants affect the integrity of cytoskeletal proteins by initiation of oxidative stress mechanisms.…”

Section: Discussionsupporting

confidence: 78%

“…For instance, it has been reported that exposure to 100 μM recombinant Tat(1-72) delays polymerization of porcine brain tubulin, and the authors suggest this occurs by competition for MAP-binding sites [10]. The interpretation of the findings by Battaglia et al [10] are supported by findings that Tat(1-72) co-immunoprecipitated with the MAP LIS1 in Tat-transfected HeLa cells [20]. Conversely, exposure of lamb brain-derived tubulin has shown facilitation of MAP-independent tubulin polymerization with exposure to the variant Tat (38-72) [17].…”

Section: Discussionmentioning

confidence: 93%

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Neurodegenerative Effects of Recombinant HIV-1 Tat(1-86) are Associated with Inhibition of Microtubule Formation and Oxidative Stress-Related Reductions in Microtubule-Associated Protein-2(a,b)

et al. 2011

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The human immunodeficiency virus 1 (HIV-1) protein Trans-activator of Transcription (Tat) is a nuclear regulatory protein that may contribute to the development of HIV-1 associated dementia by disrupting the neuronal cytoskeleton. The present studies examined effects of recombinant Tat(1-86; 1–100 nM) on microtubule-associated protein (MAP)-dependent and MAP-independent microtubule formation ex vivo and oxidative neuronal injury in rat organotypic hippocampal explants. Acute exposure to Tat(1-86) (≥1 nM) markedly reduced MAP-dependent and –independent microtubule formation ex vivo, as did vincristine sulfate (0.1–10 μM). Cytotoxicity, as measured by propidium iodide uptake, was observed in granule cells of the DG with exposure to 100 nM Tat(1-86) for 24 or 72 h, while significant reductions in MAP-2 immunoreactivity were observed in granule cells and pyramidal cells of the CA1 and CA3 regions at each timepoint. These effects were prevented by co-exposure to the soluble vitamin E analog Trolox (500 μM). Thus, effects of Tat(1-86) on the neuronal viability may be associated with direct interactions with microtubules and generation of oxidative stress.

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Section: Discussionsupporting

confidence: 78%

Section: Discussionmentioning

confidence: 93%

Neurodegenerative Effects of Recombinant HIV-1 Tat(1-86) are Associated with Inhibition of Microtubule Formation and Oxidative Stress-Related Reductions in Microtubule-Associated Protein-2(a,b)

et al. 2011

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“…The HIV-1 Tat protein, which activates transcription of HIV-1 viral genes, has been shown to induce apoptosis of T cells, in part, by virtue of distorting microtubule polymerization through its interactions with Lis1 (38, 39). Poliovirus protein 3A has been shown to exhibit anti-apoptotic activity, owing to its ability to bind and inactivate Lis1, thereby blocking membrane protein trafficking and deregulating cell division (40).…”

Section: Discussionmentioning

confidence: 99%

The Microtubule-Associated Protein Lis1 Regulates T Lymphocyte Homeostasis and Differentiation

Ngoi

Lopez

Chang

2016

The Journal of Immunology

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The microtubule-associated protein Lissencephaly 1 (Lis1) is a key regulator of cell division during stem cell renewal and differentiation. In this study, we examined the role of Lis1 in T lymphocyte homeostasis and fate diversification in response to microbial infection. T cell-specific deletion of Lis1 resulted in depletion of the peripheral CD4+ and CD8+ T lymphocyte pool, owing to a loss of homeostatic, cytokine-induced proliferation. By contrast, cognate antigen-triggered proliferation was much less affected, enabling Lis1-deficient CD8+ T cells to differentiate into terminal effector cells in response to microbial infection. Strikingly, however, the specification of Lis1-deficient long-lived memory CD8+ T lymphocytes was impaired due, in part, to an apparent failure to differentiate appropriately to IL-15. Taken together, these findings suggest that Lis1 plays an important role in T cell homeostasis and the generation of memory T lymphocytes.

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“…These results increase the differences between the behaviour of extra and intracellular Tat. Other possible explanation is that Tat localizes predominantly in the nucleus when is synthesized inside the cell, but it remains mainly at the cytosol after being endocytosed ( 17 ), where it could be retained through the binding to cytoskeletal proteins as actin, tubulin, Lis1 and Hic ( 19 , 110 , 111 ), causing higher toxicity.…”

Section: Discussionmentioning

confidence: 99%

Modifications in host cell cytoskeleton structure and function mediated by intracellular HIV-1 Tat protein are greatly dependent on the second coding exon

López-Huertas

Callejas

Abia

et al. 2010

Nucleic Acids Research

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The human immunodeficiency virus type 1 (HIV-1) regulator Tat is essential for viral replication because it achieves complete elongation of viral transcripts. Tat can be released to the extracellular space and taken up by adjacent cells, exerting profound cytoskeleton rearrangements that lead to apoptosis. In contrast, intracellular Tat has been described as protector from apoptosis. Tat gene is composed by two coding exons that yield a protein of 101 amino acids (aa). First exon (1–72aa) is sufficient for viral transcript elongation and second exon (73–101 aa) appears to contribute to non-transcriptional functions. We observed that Jurkat cells stably expressing intracellular Tat101 showed gene expression deregulation 4-fold higher than cells expressing Tat72. Functional experiments were performed to evaluate the effect of this deregulation. First, NF-κB-, NF-AT- and Sp1-dependent transcriptional activities were greatly enhanced in Jurkat-Tat101, whereas Tat72 induced milder but efficient activation. Second, cytoskeleton-related functions as cell morphology, proliferation, chemotaxis, polarization and actin polymerization were deeply altered in Jurkat-Tat101, but not in Jurkat-Tat72. Finally, expression of several cell surface receptors was dramatically impaired by intracellular Tat101 but not by Tat72. Consequently, these modifications were greatly dependent on Tat second exon and they could be related to the anergy observed in HIV-1-infected T cells.

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Untitled

Cited by 29 publications

References 43 publications

Neurodegenerative Effects of Recombinant HIV-1 Tat(1-86) are Associated with Inhibition of Microtubule Formation and Oxidative Stress-Related Reductions in Microtubule-Associated Protein-2(a,b)

Neurodegenerative Effects of Recombinant HIV-1 Tat(1-86) are Associated with Inhibition of Microtubule Formation and Oxidative Stress-Related Reductions in Microtubule-Associated Protein-2(a,b)

The Microtubule-Associated Protein Lis1 Regulates T Lymphocyte Homeostasis and Differentiation

Modifications in host cell cytoskeleton structure and function mediated by intracellular HIV-1 Tat protein are greatly dependent on the second coding exon

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