The role of nuclear lamin B1 in cell proliferation and senescence
The role of nuclear lamin B1 in cell proliferation and senescence
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DOI：
10.1101/gad.179515.111
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发表时间：
2011-12-15
影响因子：
10.5
通讯作者：
Goldman, Robert D.
中科院分区：
文献类型：
--
作者：
Shimi, Takeshi;Butin-Israeli, Veronika;Goldman, Robert D.
核纤层蛋白B1（Nuclear Lamin B1，LB 1）是细胞核的重要组成部分，参与细胞核功能的调节。本研究的结果表明，LB 1在WI-38细胞中的表达在细胞衰老过程中减少。致癌Ras诱导的早衰也通过视网膜母细胞瘤蛋白（pRb）依赖性机制降低LB 1表达。在WI-38细胞中，沉默LB 1的表达减缓细胞增殖并诱导早衰。LB 1沉默对增殖的影响需要p53的激活，而不是pRb。然而，诱导早衰需要p53和pRb两者。由沉默LB 1诱导的增殖缺陷伴随着线粒体活性氧（ROS）的p53依赖性减少，这可以通过在缺氧条件下生长来挽救。与LB 1沉默的作用相反，LB 1的过表达增加了WI-38细胞的增殖速率并延迟了衰老的开始。这种过度表达最终导致细胞周期停滞在G1/S边界。这些结果证明了LB 1在通过ROS信号通路调节人二倍体细胞增殖和衰老中的重要性。
Nuclear lamin B1 (LB1) is a major structural component of the nucleus that appears to be involved in the regulation of many nuclear functions. The results of this study demonstrate that LB1 expression in WI-38 cells decreases during cellular senescence. Premature senescence induced by oncogenic Ras also decreases LB1 expression through a retinoblastoma protein (pRb)-dependent mechanism. Silencing the expression of LB1 slows cell proliferation and induces premature senescence in WI-38 cells. The effects of LB1 silencing on proliferation require the activation of p53, but not pRb. However, the induction of premature senescence requires both p53 and pRb. The proliferation defects induced by silencing LB1 are accompanied by a p53-dependent reduction in mitochondrial reactive oxygen species (ROS), which can be rescued by growth under hypoxic conditions. In contrast to the effects of LB1 silencing, overexpression of LB1 increases the proliferation rate and delays the onset of senescence of WI-38 cells. This overexpression eventually leads to cell cycle arrest at the G1/S boundary. These results demonstrate the importance of LB1 in regulating the proliferation and senescence of human diploid cells through a ROS signaling pathway.