Accumulation of multiple forms of lamin A with down-regulation of FACE-1 suppresses growth in senescent human cells
Accumulation of multiple forms of lamin A with down-regulation of FACE-1 suppresses growth in senescent human cells
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DOI：
10.1111/j.1365-2443.2007.01057.x
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发表时间：
2007-03-01
期刊：
影响因子：
2.1
通讯作者：
Ayusawa, Dai
中科院分区：
文献类型：
--
作者：
Ukekawa, Ryo;Miki, Kensuke;Ayusawa, Dai
5-溴脱氧尿苷（BrdU）在每种细胞类型中明显诱导衰老样现象。蛋白质组学分析表明，核纤层蛋白A和C是最高度增加的HeLa细胞的细胞核后，加入BrdU。免疫印迹分析也显示核前层蛋白A的显著积累。同时，法尼基化蛋白转化酶1（FACE-1）在相同的细胞中显著下调。在经历复制性衰老的正常人成纤维细胞中也观察到类似的现象。免疫化学分析证实了上述结果。核纤层蛋白A是核纤层的主要组成部分，与多种遗传疾病有关。因此，我们异位表达了野生型，成熟型和早熟型的HeLa细胞核纤层蛋白。所有这些形式类似地抑制集落形成，并主要通过G2期延迟细胞周期进展。这些结果表明，核纤层蛋白A的量的变化，而不是其截短形式的外观，是负责受影响的细胞中的生长迟缓。
5-Bromodeoxyuridine (BrdU) clearly induces a senescence-like phenomenon in every cell type. Proteome analysis revealed that lamin A and C were most highly increased in the nuclei of HeLa cells upon addition of BrdU. Immunoblot analysis also revealed marked accumulation of nuclear prelamin A. Consistently, farnesylated-proteins converting enzyme 1 (FACE-1) was markedly down-regulated in the same cells. Similar phenomena were also observed in normal human fibroblasts undergoing replicative senescence. Immunochemical analysis confirmed the above results. Lamin A is a major component of lamina and responsible for several genetic diseases. Thus, we ectopically expressed a wild-type, a mature type and a premature type of lamin in HeLa cells. All of these forms similarly inhibited colony formation and delayed cell cycle progression mainly through G2 phase. These results suggest that a change in the amount of lamin A, rather than appearance of its truncated form, is responsible for growth retardation in affected cells.