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Statements

Subject Item
n2:RIV%2F68378050%3A_____%2F12%3A00387638%21RIV13-AV0-68378050
rdf:type
n5:Vysledek skos:Concept
dcterms:description
The biology of T-cell acute lymphoblastic leukemia (ALL) is characterized by functional pre - T-cell receptor (TCR) signaling. Non - T-cell activation linker (NTAL) is a nonenzymatic transmembrane adaptor molecule that is involved in the proximal signaling of lymphocytes. In our previous work, we found an association between high NTAL expression in T-cell ALL blasts and a favorable response to initial glucocorticoid treatment. In the present study, we confirm our previous observation in an experimental model. In addition, the molecular mechanism of the contribution of NTAL to malignant T-cell ALL blast signaling and to methylprednisolone-induced cell death is analyzed. In the in vitro experiments, we used the T-cell ALL Jurkat cell line (Jurkat/wt) and derived Jurkat cell line with stable NTAL expression (Jurkat/NTAL(+)). Cell signaling and cell death after methylprednisolone treatment and after TCR stimulation were analyzed using flow cytometry, Western blot, and quantitative polymerase chain reaction. Jurkat/NTAL(+) cells are significantly more sensitive to both methyl prednisolone treatment and TCR-induced stimulation. In addition, after TCR stimulation, Jurkat/NTAL(+) cells show a higher level of intracellular extracellular signal-regulated kinase 1/2 (ERK) phosphorylation and increased expression of the CD69 activation marker on the cell surface than the Jurkat/wt cells. The ERK inhibitor U0126 almost completely abrogates TCR-induced cell death and, importantly, reverses the sensitizing effect of the NTAL protein on methylprednisolone-induced cell death. In conclusion, NTAL acts as a tumor suppressor that enhances the proximal signaling of leukemic blasts. The key downstream molecule responsible for the biological effect of TCR signaling is ERK. Higher ERK phosphorylation leads to enhanced cell death after TCR stimulation and increases cell sensitivity to methylprednisolone-induced cell death. The biology of T-cell acute lymphoblastic leukemia (ALL) is characterized by functional pre - T-cell receptor (TCR) signaling. Non - T-cell activation linker (NTAL) is a nonenzymatic transmembrane adaptor molecule that is involved in the proximal signaling of lymphocytes. In our previous work, we found an association between high NTAL expression in T-cell ALL blasts and a favorable response to initial glucocorticoid treatment. In the present study, we confirm our previous observation in an experimental model. In addition, the molecular mechanism of the contribution of NTAL to malignant T-cell ALL blast signaling and to methylprednisolone-induced cell death is analyzed. In the in vitro experiments, we used the T-cell ALL Jurkat cell line (Jurkat/wt) and derived Jurkat cell line with stable NTAL expression (Jurkat/NTAL(+)). Cell signaling and cell death after methylprednisolone treatment and after TCR stimulation were analyzed using flow cytometry, Western blot, and quantitative polymerase chain reaction. Jurkat/NTAL(+) cells are significantly more sensitive to both methyl prednisolone treatment and TCR-induced stimulation. In addition, after TCR stimulation, Jurkat/NTAL(+) cells show a higher level of intracellular extracellular signal-regulated kinase 1/2 (ERK) phosphorylation and increased expression of the CD69 activation marker on the cell surface than the Jurkat/wt cells. The ERK inhibitor U0126 almost completely abrogates TCR-induced cell death and, importantly, reverses the sensitizing effect of the NTAL protein on methylprednisolone-induced cell death. In conclusion, NTAL acts as a tumor suppressor that enhances the proximal signaling of leukemic blasts. The key downstream molecule responsible for the biological effect of TCR signaling is ERK. Higher ERK phosphorylation leads to enhanced cell death after TCR stimulation and increases cell sensitivity to methylprednisolone-induced cell death.
dcterms:title
The adaptor protein NTAL enhances proximal signaling and potentiates corticosteroid-induced apoptosis in T-ALL The adaptor protein NTAL enhances proximal signaling and potentiates corticosteroid-induced apoptosis in T-ALL
skos:prefLabel
The adaptor protein NTAL enhances proximal signaling and potentiates corticosteroid-induced apoptosis in T-ALL The adaptor protein NTAL enhances proximal signaling and potentiates corticosteroid-induced apoptosis in T-ALL
skos:notation
RIV/68378050:_____/12:00387638!RIV13-AV0-68378050
n5:predkladatel
n6:ico%3A68378050
n3:aktivita
n7:P n7:Z n7:I
n3:aktivity
I, P(2B06064), P(NS10473), Z(MSM0021620813)
n3:cisloPeriodika
5
n3:dodaniDat
n10:2013
n3:domaciTvurceVysledku
n20:7171390 n20:9394265
n3:druhVysledku
n8:J
n3:duvernostUdaju
n13:S
n3:entitaPredkladatele
n18:predkladatel
n3:idSjednocenehoVysledku
121074
n3:idVysledku
RIV/68378050:_____/12:00387638
n3:jazykVysledku
n19:eng
n3:klicovaSlova
acute lymphoblastic leukemia; TCR signaling; NTAL; ERK
n3:klicoveSlovo
n9:ERK n9:TCR%20signaling n9:NTAL n9:acute%20lymphoblastic%20leukemia
n3:kodStatuVydavatele
US - Spojené státy americké
n3:kontrolniKodProRIV
[BF51F0A607C1]
n3:nazevZdroje
Experimental Hematology
n3:obor
n17:EB
n3:pocetDomacichTvurcuVysledku
2
n3:pocetTvurcuVysledku
6
n3:projekt
n14:NS10473 n14:2B06064
n3:rokUplatneniVysledku
n10:2012
n3:svazekPeriodika
40
n3:tvurceVysledku
Kalina, T. Brdička, Tomáš Zuna, J. Kanderová, V. Skopcová, Tereza Svojgr, K.
n3:wos
000303301100003
n3:zamer
n4:MSM0021620813
s:issn
0301-472X
s:numberOfPages
7
n16:doi
10.1016/j.exphem.2012.01.011