Lysosome-mediated processing of chromatin in senescence.
Lysosome-mediated processing of chromatin in senescence.
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DOI：
10.1083/jcb.201212110
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发表时间：
2013-07-08
期刊：
影响因子：
--
通讯作者：
Adams PD
中科院分区：
文献类型：
--
作者：
Ivanov A;Pawlikowski J;Manoharan I;van Tuyn J;Nelson DM;Rai TS;Shah PP;Hewitt G;Korolchuk VI;Passos JF;Wu H;Berger SL;Adams PD
衰老细胞将染色质片段从细胞核挤出到细胞质中，在细胞质中它们通过自噬/溶酶体途径进行加工。细胞衰老是一种稳定的增殖停滞，一种有效的肿瘤抑制机制，并且是组织衰老的可能贡献者。细胞衰老涉及广泛的细胞重塑，包括染色质结构的重塑。自噬和溶酶体对于细胞成分的再循环和细胞重塑是重要的。在这里，我们表明，自噬/溶酶体途径的过程中染色质衰老细胞。在衰老细胞中，核纤层蛋白A/C阴性，但强烈的γ-H2 AX阳性和H3 K27 me 3阳性，细胞质染色质片段（CCF）从核出芽，这与核纤层蛋白B1下调和核膜完整性丧失有关。在细胞质中，CCF被自噬机制靶向。衰老细胞表现出溶酶体介导的组蛋白的蛋白水解加工的标记物，并且以溶酶体依赖性的方式逐渐耗尽总组蛋白含量。在体内，组蛋白的消耗与痣成熟相关，这是一个与增殖停滞和临床良性相关的既定组织病理学参数。我们的结论是，衰老细胞通过自噬/溶酶体途径处理其染色质，这可能有助于稳定衰老和肿瘤抑制。
Senescent cells extrude fragments of chromatin from the nucleus into the cytoplasm, where they are processed by an autophagic/lysosomal pathway. Cellular senescence is a stable proliferation arrest, a potent tumor suppressor mechanism, and a likely contributor to tissue aging. Cellular senescence involves extensive cellular remodeling, including of chromatin structure. Autophagy and lysosomes are important for recycling of cellular constituents and cell remodeling. Here we show that an autophagy/lysosomal pathway processes chromatin in senescent cells. In senescent cells, lamin A/C–negative, but strongly γ-H2AX–positive and H3K27me3-positive, cytoplasmic chromatin fragments (CCFs) budded off nuclei, and this was associated with lamin B1 down-regulation and the loss of nuclear envelope integrity. In the cytoplasm, CCFs were targeted by the autophagy machinery. Senescent cells exhibited markers of lysosomal-mediated proteolytic processing of histones and were progressively depleted of total histone content in a lysosome-dependent manner. In vivo, depletion of histones correlated with nevus maturation, an established histopathologic parameter associated with proliferation arrest and clinical benignancy. We conclude that senescent cells process their chromatin via an autophagy/lysosomal pathway and that this might contribute to stability of senescence and tumor suppression.
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3.3
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影响因子：
21.3
作者：
Di Micco R;Sulli G;Dobreva M;Liontos M;Botrugno OA;Gargiulo G;dal Zuffo R;Matti V;d'Ario G;Montani E;Mercurio C;Hahn WC;Gorgoulis V;Minucci S;d'Adda di Fagagna F
通讯作者：
d'Adda di Fagagna F