Parasite-mediated nuclear factor κB regulation in lymphoproliferation caused by<i>Theileria parva</i> infection

Palmer, Guy H.; Machado, Joel; Fernández, Paula; Heussler, Volker; Perinat, Therese; Dobbelaere, Dirk

doi:10.1073/pnas.94.23.12527

Cited by 71 publications

(55 citation statements)

References 54 publications

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“…As has also been shown in other systems, TPCK potently inhibited NF-kB DNA binding activity in a dose dependent manner ( Figure 4A). In agreement with earlier observations, 41 NAC did not inhibit NF-kB DNA binding. In TPCK-treated cells, however, NF-kB DNA binding was restored to a large extent, albeit not completely, in the presence of NAC.…”

Section: Effects Of Tpck and Nac On Ikb Phosphorylation In Tpi T-cellssupporting

confidence: 82%

“…IkBb is phosphorylated in Tpi T-cells and TPCK treatment also resulted in deficient IkBb phosphorylation as is evident from the appearance of IkBb forms with lower molecular weight ( Figure 3A, upper panel). Alterations in IkBb phosphorylation were also obvious within 1 h. As we have demonstrated previously, 41 NAC did not affect IkB. A consistent feature observed for both IkBa and IkBb, however, was that the inhibition of phosphorylation by TPCK was completely prevented by treatment with NAC.…”

Section: Effects Of Tpck and Nac On Ikb Phosphorylation In Tpi T-cellssupporting

confidence: 56%

“…For this purpose we used the Tpi T-cell line in which NF-kB is constitutively activated 40 through a mechanism which involves the continuous degradation of both IkBa and IkBb. 41 As IkBa itself is transcriptionally regulated by NF-kB, 42,43 increased IkBa levels can be found in Tpi T-cells, despite its constitutive turnover. 41 Phosphorylated IkBa migrates with reduced electrophoretic mobility and is readily detected in untreated Tpi T-cells ( Figure 3A, lower panel).…”

Section: Effects Of Tpck and Nac On Ikb Phosphorylation In Tpi T-cellsmentioning

confidence: 99%

“…41 As IkBa itself is transcriptionally regulated by NF-kB, 42,43 increased IkBa levels can be found in Tpi T-cells, despite its constitutive turnover. 41 Phosphorylated IkBa migrates with reduced electrophoretic mobility and is readily detected in untreated Tpi T-cells ( Figure 3A, lower panel). Culturing Tpi T-cells in the presence of TPCK prevented IkBa phosphorylation as judged by the disappearance of the slower migrating IkBa form.…”

Section: Effects Of Tpck and Nac On Ikb Phosphorylation In Tpi T-cellsmentioning

confidence: 99%

“…40,41 Electrophoretic mobility shift assays (EMSA) were performed, using oligonucleotides corresponding to the HIV-LTR kB motif which bind complexes consisting of p65 and p50 in Tpi T-cells (J.M. unpublished observation).…”

Section: Effects Of Tpck and Nac On Ikb Phosphorylation In Tpi T-cellsmentioning

confidence: 99%

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N-acetylcysteine blocks apoptosis induced by N-α-tosyl-L-phenylalanine chloromethyl ketone in transformed T-cells

et al. 1999

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The serine protease inhibitor N-a-tosyl-L-phenylalanine chloromethyl ketone (TPCK) can interfere with cell-cycle progression and has also been shown either to protect cells from apoptosis or to induce apoptosis. We tested the effect of TPCK on two transformed T-cell lines. Both Jurkat T-cells and Theileria parva-transformed T-cells were shown to be highly sensitive to TPCK-induced growth arrest and apoptosis. Surprisingly, we found that the thiol antioxidant, Nacetylcysteine (NAC), as well as L-or D-cysteine blocked TPCK-induced growth arrest and apoptosis. TPCK inhibited constitutive NF-kB activation in T. parva-transformed T-cells, with phosphorylation of IkBa and IkBb being inhibited with different kinetics. TPCK-mediated inhibition of IkB phosphorylation, NF-kB DNA binding and transcriptional activity were also prevented by NAC or cysteine. Our observations indicate that apoptosis and NF-kB inhibition induced by TPCK result from modifications of sulphydryl groups on proteins involved in regulating cell survival and the NF-kB activation pathway(s).

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Section: Effects Of Tpck and Nac On Ikb Phosphorylation In Tpi T-cellssupporting

confidence: 82%

Section: Effects Of Tpck and Nac On Ikb Phosphorylation In Tpi T-cellssupporting

confidence: 56%

Section: Effects Of Tpck and Nac On Ikb Phosphorylation In Tpi T-cellsmentioning

confidence: 99%

Section: Effects Of Tpck and Nac On Ikb Phosphorylation In Tpi T-cellsmentioning

confidence: 99%

Section: Effects Of Tpck and Nac On Ikb Phosphorylation In Tpi T-cellsmentioning

confidence: 99%

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N-acetylcysteine blocks apoptosis induced by N-α-tosyl-L-phenylalanine chloromethyl ketone in transformed T-cells

et al. 1999

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Theileria

and

Baumgärtner

2009

Intracellular Niches of Microbes

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Initiation of translation and cellular localization of Theileria annulata casein kinase IIα: Implication for its role in host cell transformation

Biermann

Schnittger

Beyer

et al. 2003

Journal Cellular Physiology

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Theileria annulata and T. parva are protozoa that infect bovine leukocytes which leads to subsequent transformation and uncontrolled proliferation of these cells. It has been proposed that the CKIIalpha subunit of T. parva induces mitogenic pathways of host leukocytes by being exported into the host cell. The evidence for this is the existence of a predicted N-terminal secretion signal-like peptide. We tested this hypothesis by analyzing gene structure, translation, and protein localization of the T. annulata CKIIalpha (TaCKIIalpha). The determined TaCKIIalpha-ORF potentially codes for a 50 kDa protein with an N-terminal extension including a possible signal sequence not present in CKIIalpha proteins of non-Theileria species. However, antisera raised against TaCKIIalpha recognized a protein of a molecular weight of about 40 kDa and, therefore, inconsistent with this predicted molecular weight. We demonstrate by in vitro transcription/translation that this discrepancy is due to translation from a downstream initiation site omitting the putative N-terminal signal sequence and thus excluding the notion that the protein product is secreted via the classical secretory pathway. In corroboration immunofluorescence investigations suggest that the TaCKIIalpha subunit is confined to the parasite schizonts within the host cell. On the basis of the above findings it seems highly unlikely that export via the classical pathway of the parasite CKIIalpha is the way in which this protein possibly contributes to host cell transformation.

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Parasite-mediated nuclear factor κB regulation in lymphoproliferation caused byTheileria parva infection

Cited by 71 publications

References 54 publications

N-acetylcysteine blocks apoptosis induced by N-α-tosyl-L-phenylalanine chloromethyl ketone in transformed T-cells

N-acetylcysteine blocks apoptosis induced by N-α-tosyl-L-phenylalanine chloromethyl ketone in transformed T-cells

Theileria

Initiation of translation and cellular localization of Theileria annulata casein kinase IIα: Implication for its role in host cell transformation

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