CD73 participates in cellular multiresistance program and protects against TRAIL-induced apoptosis.
CD73 participates in cellular multiresistance program and protects against TRAIL-induced apoptosis.
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DOI：
10.4049/jimmunol.181.1.464
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发表时间：
2008-07-01
期刊：
影响因子：
--
通讯作者：
Eriksson JE
中科院分区：
文献类型：
--
作者：
Mikhailov A;Sokolovskaya A;Yegutkin GG;Amdahl H;West A;Yagita H;Lahesmaa R;Thompson LF;Jalkanen S;Blokhin D;Eriksson JE
白血病和其他癌细胞的多重耐药表型的分子机制尚未完全了解。我们使用表达阵列来揭示抗白血病T细胞白血病克隆（A4）和正常抗白血病敏感的亲本Jurkat细胞的基因表达谱的差异。CD 73（ecto-5′-nucleotidase）基因在耐药A4细胞克隆中表达上调最多。A4细胞表面表达CD 73，并具有明显的胞外5′-核苷酸酶活性。通过将野生型CD 73转染到天然Jurkat细胞中证实了CD 73的作用，这导致了对TRAIL诱导的凋亡的特异性抗性，但不是其他类型的凋亡。通过小干扰RNA介导的CD 73下调，恢复TRAIL敏感性，进一步证实了CD 73的保护作用。CD 73介导的抗性不依赖于CD 73的酶活性，但依赖于蛋白质通过GPI锚定到膜上。我们认为TRAIL信号的抑制作用是通过CD 73与死亡受体5的相互作用来实现的，因为CD 73和死亡受体5可以被免疫共沉淀，并且通过共聚焦显微镜显示在质膜中共定位。我们认为CD 73是多抗性机制的一个组成部分，其转录在免疫系统的选择性压力下被激活。
The molecular mechanisms underlying the multiresistant phenotype of leukemic and other cancer cells are incompletely understood. We used expression arrays to reveal differences in the gene expression profiles of an apoptosis-resistant T cell leukemia clone (A4) and normally apoptosis-sensitive parental Jurkat cells. CD73 (ecto-5′-nucleotidase) was the most up-regulated gene in the resistant A4 cell clone. A4 cells displayed CD73 surface expression and significant ecto-5′-nucleotidase activity. The role of CD73 was confirmed by transfection of wild-type CD73 into native Jurkat cells, which led to specific resistance against TRAIL-induced apoptosis, but not other types of apoptosis. The protective role of CD73 was further confirmed by small interfering RNA-mediated down-regulation of CD73, restoring TRAIL sensitivity. CD73-mediated resistance was independent of enzymatic activity of CD73, but was reliant on the anchoring of the protein to the membrane via GPI. We suggest that the inhibition of TRAIL signaling works through interaction of CD73 with death receptor 5, as CD73 and death receptor 5 could be coimmunoprecipitated and were shown to be colocalized in the plasma membrane by confocal microscopy. We propose that CD73 is a component of multiresistance machinery, the transcription of which is activated under selective pressure of the immune system.
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影响因子：
15.9
作者：
Castrop, H;Huang, YN;Schnermann, J
通讯作者：
Schnermann, J
影响因子：
4.8
作者：
Gajate, C;Mollinedo, F
通讯作者：
Mollinedo, F
DOI：
10.1083/jcb.143.5.1353
发表时间：
1998-11-30
期刊：
The Journal of cell biology
影响因子：
--
作者：
Kawahara A;Ohsawa Y;Matsumura H;Uchiyama Y;Nagata S
通讯作者：
Nagata S
影响因子：
4.8
作者：
Boesen-de Cock, JGR;Tepper, AD;Borst, J
通讯作者：
Borst, J
影响因子：
4.3
作者：
GUTENSOHN, W;RESTA, R;THOMPSON, LF
通讯作者：
THOMPSON, LF