The herpes simplex virus type 1 (HSV-1) latency-associated transcript (LAT) protects cells against cold-shock-induced apoptosis by maintaining phosphorylation of protein kinase B (AKT).

The herpes simplex virus type 1 (HSV-1) latency-associated transcript (LAT) protects cells against cold-shock-induced apoptosis by maintaining phosphorylation of protein kinase B (AKT).
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DOI:
10.1007/s13365-015-0361-z
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发表时间:
2015-10
影响因子:
3.2
通讯作者:
Wechsler SL
Wechsler SL
中科院分区:
医学4区
文献类型:
--
作者:
Carpenter D;Hsiang C;Jiang X;Osorio N;BenMohamed L;Jones C;Wechsler SL

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单纯疱疹病毒1型(HSV-1)潜伏相关转录本(LAT)阻断细胞凋亡并抑制caspase-3活化。我们以前表明,血清饥饿(从组织培养基中去除血清),这需要几天时间来诱导细胞凋亡,导致AKT(蛋白激酶B)和磷酸化AKT(pAKT)在不表达LAT的细胞中的水平降低。相反,在小鼠神经母细胞瘤细胞中,表达LAT、AKT和pAKT的水平仍然很高。AKT是促进细胞存活的丝氨酸/苏氨酸蛋白激酶。为了使用不同且更快速的诱导细胞凋亡的方法来检查LAT对AKT-pAKT的影响,将表达LAT的稳定细胞系与从冷休克诱导的细胞凋亡恢复后15分钟的非LAT表达细胞进行比较。LAT的表达似乎抑制pAKT的去磷酸化。这种保护作用与阻断许多被pAKT抑制的促凋亡事件相关。这些结果支持这样的假设,即抑制pAKT的去磷酸化可能是LAT保护细胞免于凋亡的途径之一。
The herpes simplex virus type 1 (HSV-1) latency-associated transcript (LAT) blocks apoptosis and inhibits caspase-3 activation. We previously showed that serum starvation (removal of serum from tissue culture media), which takes several days to induce apoptosis, results in decreased levels of both AKT (protein kinase B) and phosphorylated AKT (pAKT) in cells not expressing LAT. In contrast in mouse neuroblastoma cells expressing LAT, AKT, and pAKT levels remained high. AKT is a serine/threonine protein kinase that promotes cell survival. To examine the effect of LAT on AKT-pAKT using a different and more rapid method of inducing apoptosis, a stable cell line expressing LAT was compared to non-LAT expressing cells as soon as 15 min following recovery from cold-shock-induced apoptosis. Expression of LAT appeared to inhibit dephosphorylation of pAKT. This protection correlated with blocking numerous pro-apoptotic events that are inhibited by pAKT. These results support the hypothesis that inhibiting dephosphorylation of pAKT may be one of the pathways by which LAT protects cells against apoptosis.