Cell Death Dis. 2019 Jan 30;10(2):94. doi: 10.1038/s41419-019-1369-8.
Downregulation of G2/mitotic-specific cyclinB1 triggers autophagy via AMPK-ULK1-dependent signal pathway in nasopharyngeal carcinoma cells.
Xie X1, Lin W2, Zheng W2, Chen T2, Yang H2, Sun L2, Huang F3, Wang Z2, Lin H2, Chen L4, Liu J3, Yang L5.
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Abstract
CyclinB1 is a regulatory protein involved in mitosis. Multiple lines of evidence indicate that cyclinB1 depletion constrains proliferation and induces apoptosis in human tumor cells. The cells become susceptible to suffer a critical situation when cyclinB1 is downregulated. Autophagy is a major intracellular degradation system that recycles nutrients, removes damaged organelles, and promotes cell survival under stressful conditions, whereas the role of autophagy in cyclinB1-deprived neoplastic cell as well as the underlying molecular mechanism remains obscure. Here we pioneeringly elaborated that specific knockdown of cyclinB1 triggered autophagy via AMPK-ULK1-dependent signal pathway through the elevation of ROS, rather than ATP in the cell lines of CNE-1 and CNE-2. Moreover, ROS scavengers demonstrated that the observed effect of cyclinB1 silencing on AMPK phosphorylation was ROS dependent. Additionally, double knockdown of AMPK and cyclinB1 evidently abrogated cyclinB1 silencing-induced autophagy. Summarily, this study first revealed that downregulation of cyclinB1 induced autophagy via AMPK-ULK1-dependent signal pathway, which represents a key step toward unveiling the mechanism how cell cycle checkpoint proteins regulate autophagy.
PMID: 30700698 PMCID: PMC6353984 DOI: 10.1038/s41419-019-1369-8
