p53-Mediated Molecular Control of Autophagy in Tumor Cells.
p53-Mediated Molecular Control of Autophagy in Tumor Cells.
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DOI：
10.3390/biom8020014
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发表时间：
2018-03-21
期刊：
影响因子：
5.5
通讯作者：
Fröhlich LF
中科院分区：
文献类型：
--
作者：
Mrakovcic M;Fröhlich LF
自噬是真核细胞不可或缺的机制，促进细胞成分的去除和更新，从而平衡细胞的能量消耗和稳态。自噬的失调现在被认为是促成肿瘤发展的特征性关键特征之一。近年来，抑制自噬结合化疗治疗已被视为癌症治疗的新疗法。然而，根据癌症的类型和背景，干扰自噬机制可以促进或破坏肿瘤发生。因此，揭示调控自噬和控制肿瘤发生的主要信号通路至关重要。到目前为止，一些肿瘤抑制蛋白和癌基因已经成为自噬的重要调节因子，它们的缺失或突变有利于肿瘤的形成。哺乳动物细胞“看门人”p53属于这些肿瘤抑制因子中最常见的人类肿瘤突变之一。过去十年的实验证据令人信服地报告，p53可以作为自噬的激活剂或抑制剂，这取决于其亚细胞定位和作用模式。这一发现获得了特别的意义，因为p53缺陷或在肿瘤细胞的细胞质中积累的p53的突变变体能够激活自噬。因此，我们最近确定p53作为一个分子枢纽，调节自噬和凋亡组蛋白去乙酰化酶处理的子宫肉瘤细胞。鉴于这一新的实验证据，在这篇综述中，我们将重点放在p53信号作为肿瘤细胞自噬通路的介导者。
Autophagy is an indispensable mechanism of the eukaryotic cell, facilitating the removal and renewal of cellular components and thereby balancing the cell’s energy consumption and homeostasis. Deregulation of autophagy is now regarded as one of the characteristic key features contributing to the development of tumors. In recent years, the suppression of autophagy in combination with chemotherapeutic treatment has been approached as a novel therapy in cancer treatment. However, depending on the type of cancer and context, interference with the autophagic machinery can either promote or disrupt tumorigenesis. Therefore, disclosure of the major signaling pathways that regulate autophagy and control tumorigenesis is crucial. To date, several tumor suppressor proteins and oncogenes have emerged as eminent regulators of autophagy whose depletion or mutation favor tumor formation. The mammalian cell “janitor” p53 belongs to one of these tumor suppressors that are most commonly mutated in human tumors. Experimental evidence over the last decade convincingly reports that p53 can act as either an activator or an inhibitor of autophagy depending on its subcellular localization and its mode of action. This finding gains particular significance as p53 deficiency or mutant variants of p53 that accumulate in the cytoplasm of tumor cells enable activation of autophagy. Accordingly, we recently identified p53 as a molecular hub that regulates autophagy and apoptosis in histone deacetylase inhibitor-treated uterine sarcoma cells. In light of this novel experimental evidence, in this review, we focus on p53 signaling as a mediator of the autophagic pathway in tumor cells.
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影响因子：
13.3
作者：
Crighton, Diane;Wilkinson, Simon;Ryan, Kevin M.
通讯作者：
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影响因子：
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DOI：
10.1016/j.biocel.2007.07.020
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