S6K1 controls autophagosome maturation in autophagy induced by sulforaphane or serum deprivation
S6K1 controls autophagosome maturation in autophagy induced by sulforaphane or serum deprivation
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DOI：
10.1016/j.ejcb.2015.05.001
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发表时间：
2015-10-01
影响因子：
6.6
通讯作者：
Herman-Antosiewicz, Anna
中科院分区：
文献类型：
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作者：
Hac, Aleksandra;Domachowska, Anna;Herman-Antosiewicz, Anna
已经确定mTORC 1通过磷酸化和自噬体形成相关蛋白的失活抑制自噬。然而，其底物p7056激酶1（S6 K1）在自噬中的作用是相当有争议的。在一些模型中，S6 K1活性与自噬抑制相关，然而，其他一些研究表明，S6 K1促进而不是抑制这一过程。在这里，我们研究了S6 K1在前列腺癌细胞（PC-3）和非癌性小鼠胚胎成纤维细胞（MEF）中的作用，无论是用自噬诱导剂萝卜硫素（一种来自十字花科植物的异硫氰酸酯）处理，还是剥夺血清。我们的研究结果表明，组成型活性S6 K1降低了用萝卜硫素处理的细胞中自噬体空泡的LC 3加工和病灶形成的水平。另一方面，S6 K1的存在对于在由萝卜硫素或血清剥夺诱导的自噬条件下的自噬体成熟是必需的。S6 K1水平的降低或S6激酶的缺乏导致自噬体的积累和自噬溶酶体数量的下降，从而在应激条件下干扰自噬通量。此外，缺乏S6激酶会降低细胞在应激条件下的存活率。(C)2015 Elsevier GmbH. All rights reserved.
It is well established that mTORC1 suppresses autophagy by phosphorylation and inactivation of proteins involved in autophagosome formation. However, the role of its substrate, p7056 kinasel (S6K1), in autophagy is quite controversial. In some models S6K1 activity correlates with autophagy suppression, however, some other studies show that S6K1 promotes rather than inhibits this process. Here, we investigated the role of S6K1 in prostate cancer cells (PC-3) and non-cancerous, mouse embryonic fibroblasts (MEF), either treated with autophagy inducer sulforaphane, an isothiocyanate derived from cruciferous plants, or deprived of serum. Our results indicate that constitutively active S6K1 decreases the level of LC3 processing and foci formation by autophagosomal vacuoles in cells treated with sulforaphane. On the other hand, presence of S6K1 is necessary for autophagosome maturation under conditions of autophagy induced by either sulforaphane or serum deprivation. Diminished level of S6K1 or lack of S6 kinases results in both, accumulation of autophagosomes and drop in the autophagolysosome number, and thus disturbs autophagy flux under stress conditions. Moreover, lack of S6 kinases reduces cell survival under stress conditions. (C) 2015 Elsevier GmbH. All rights reserved.