Senescence-associated alterations of cytoskeleton: extraordinary production of vimentin that anchors cytoplasmic p53 in senescent human fibroblasts
Senescence-associated alterations of cytoskeleton: extraordinary production of vimentin that anchors cytoplasmic p53 in senescent human fibroblasts
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DOI：
10.1007/s00418-005-0766-5
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发表时间：
2005-03-01
影响因子：
2.3
通讯作者：
Inoue, A
中科院分区：
文献类型：
--
作者：
Nishio, K;Inoue, A
用衰老和年轻成纤维细胞系统地研究了衰老细胞的细胞骨架。在细胞衰老过程中，皮肤成纤维细胞显著产生静脉蛋白，而肌动蛋白和微管蛋白则下调。在局灶黏附蛋白中，paxillin和c-Src也减少。衰老细胞形成了长而致密的静脉蛋白网络、长而细的肌动蛋白纤维和许多小的局灶接触点，而年轻细胞则形成了短而粗的肌动蛋白应力纤维和明显大的局灶粘连。值得注意的是，衰老的成纤维细胞明显产生p53分子，并将其固定在细胞质中的静脉蛋白细胞骨架上。用特异性识别p53构象变体的抗体PAb240检测了vimentin-锚定p53。通过转染表达了gfp标记的野生型p53 cDNA，并且在衰老细胞的细胞质中也保留了p53，这表明p53经过结构修饰，可以被PAb240识别并锚定在波形蛋白丝上。我们讨论了细胞骨架的显著改变与衰老细胞增殖和迁移减少的相关性，以及肿瘤抑制因子p53的细胞骨架锚定的意义。
The cytoskeleton of senescent cells was systematically studied using senescent and young fibroblasts. In the cell senescence, skin fibroblasts extraordinarily produced vimentin in contrast to actin and tubulin, which were down-regulated. Among the focal adhesion proteins, paxillin and c-Src decreased also. Senescent cells developed a long and dense vimentin network, long and thin actin fibers, and numerous small focal contact sites, which contrasted with young cells with short and thick actin stress fibers and prominently large focal adhesions. Noticeably, senescent fibroblasts markedly produced p53 molecules and anchored them to vimentin-cytoskeleton in the cytoplasm. The vimentin-anchored p53 was detected with antibody PAb240 that specifically recognizes a conformation variant of p53. A GFP-tagged wild type p53 cDNA was expressed by transfection and shown also to be retained in the cytoplasm in senescent cells, suggesting that p53 is structurally modified to be recognized by PAb240 and anchored to vimentin filaments. We discuss the correlation of the marked alteration of cytoskeleton and senescent cells' diminished proliferation and migration, as well as the significance of cytoskeletal anchorage of tumor suppressor p53.