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CaMKK?-AMPK?2 signaling contributes to mitotic Golgi fragmentation and the G2/M transition in mammalian cells.


ABSTRACT: Before a cell enters mitosis, the Golgi apparatus undergoes extensive fragmentation. This is required for the correct partitioning of the Golgi apparatus into daughter cells, and inhibition of this process leads to cell cycle arrest in G2 phase. AMP-activated protein kinase (AMPK) plays critical roles in regulating growth and reprogramming metabolism. Recent studies have suggested that AMPK promotes mitotic progression and Golgi disassembly, and that this seems independent of the cellular energy status. However, the molecular mechanism underlying these events is not well understood. Here, we show that both treatment with compound C and depletion of AMPK?2 (but not AMPK?1) delays the G2/M transition in synchronized HeLa cells, as evidenced by flow cytometry and mitotic index analysis. Furthermore, knockdown of AMPK?2 specifically delays further fragmentation of isolated Golgi stacks. Interestingly, pAMPK?(Thr172) signals transiently appear in the perinuclear region of late G2/early prophase cells, partially co-localizing with the Golgi matrix protein, GM-130. These Golgi pAMPK?(Thr172) signals were also specifically abolished by AMPK?2 knockdown, indicating specific spatio-temporal activation of AMPK?2 at Golgi complex during late G2/early prophases. We also found that the specific CaMKK? inhibitor, STO-609, reduces the pAMPK? (Thr172) signals in the perinuclear region of G2 phase cells and delays mitotic Golgi fragmentation. Taken together, these data suggest that AMPK?2 is the major catalytic subunit of AMPK? which regulates Golgi fragmentation and G2/M transition, and that the CaMKK? activates AMPK?2 during late G2 phase.

SUBMITTER: Lee IJ 

PROVIDER: S-EPMC4614108 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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CaMKKβ-AMPKα2 signaling contributes to mitotic Golgi fragmentation and the G2/M transition in mammalian cells.

Lee In Jeong IJ   Lee Chang-Woo CW   Lee Jae-Ho JH  

Cell cycle (Georgetown, Tex.) 20150101 4


Before a cell enters mitosis, the Golgi apparatus undergoes extensive fragmentation. This is required for the correct partitioning of the Golgi apparatus into daughter cells, and inhibition of this process leads to cell cycle arrest in G2 phase. AMP-activated protein kinase (AMPK) plays critical roles in regulating growth and reprogramming metabolism. Recent studies have suggested that AMPK promotes mitotic progression and Golgi disassembly, and that this seems independent of the cellular energy  ...[more]

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