VL30 retrotransposition signals activation of a caspaseindependent and p53-dependent death pathway associated with mitochondrial and lysosomal damage

长终端重复(LTR ) 的影响房间命运上的 retrotransposition 是未知的。这里，我们在转变 SV40 的老鼠 SVTT1 房间在房间死亡上调查了 VL30 retrotransposition 的效果。VL30 retrotransposon 的 Transfection 减少了由 17 褶层的 SVTT1 的 clonogenicity，作为与父母 NIH3T3 房间相比。频率和房间死亡率在 retrotransposition 积极的 SVTT1 被发现的 retrotransposition 的相关层次克隆房间，展出 DNA 破碎，原子冷凝作用， multinucleation 和细胞质的 vacuolization。受动器 caspases 的激活的分析揭示了 caspase 独立的房间死亡机制。然而，房间死亡与感应的 p53 和 Bcl-2 和 Hsp70 蛋白质表示的美洲狮伪和 Bax 和 downregulation 的伴随物 upregulation 被联系。而且，我们发现了大 T 抗原(副)/p53 和 p53 translocation 的 colocalization 的部分损失到线粒体，导致外部膜 permeabilization (MOMP ) 由 lysosomal 膜 permeabilization (LMP ) 伴随了的 mitochondrial。有趣地，有抗氧化剂 N-acetylcysteine 的处理废除了细胞死亡，建议导出 mitochondrial 的反应的氧种类的参与，并且导致了 retrotransposition 频率的增加。重要地，当 VL30 动员被导致，房间死亡的正式就职是 retrotransposon 特定的 VL30；相反， non-LTR L1 的动员(LINE-1，长散布的原子 element-1 ) ， B2 和 LTR MusD retrotransposons 减少了。第一次，我们的结果提供 VL30 retrotransposition 调停的充分证据经由 mitochondrial 和 lysosomal 损坏的房间死亡，揭开是的 retrotransposition 的角色在触发房间死亡激活 mitochondrial-lysosomal 串音的一个原子信号。

Cytoplasmic L1 Levels in Cancer

In addition to shaping genome diversification over evolutionary time, L1 retrotransposition alters gene expression as well. The most notable gene altering process involves insertional mutagenesis. The aim of the study was the examination of both nuclear L1 expression levels and cellular localization in cancer cell lines, PBMCs from healthy volunteers and PBMCs from cancer patients. L1 was detected by FISH in chromosome preparations. L1 probe was custom-made using end-point PCR against L1-ORF2 and conjugated with FITC. It was found that cancer cell lines and clinical samples from cancer patients contained significantly elevated levels of L1 per nucleus compared to healthy volunteers. Cytoplasmic L1 was also increased in the above mentioned samples denoting that cancer could be associated with increased L1 activation and mobility. Our results may provide a novel cancer diagnostic marker and highlight the possibility of cytoplasmic L1 inhibition as a therapeutic intervention for cancer.