The STIM1-Orai1 pathway of store-operated Ca2+ entry controls the checkpoint in cell cycle G1/S transition

Yun Wen Chen, Yih Fung Chen, Ying Ting Chen, Wen Tai Chiu, Meng Ru Shen

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Ca2+ signaling is important to trigger the cell cycle progression, while it remains elusive in the regulatory mechanisms. Here we show that store-operated Ca2+ entry (SOCE), mediated by the interaction between STIM1 (an endoplasmic reticulum Ca2+ sensor) and Orai1 (a cell membrane pore structure), controls the specific checkpoint of cell cycle. The fluctuating SOCE activity during cell cycle progression is universal in different cell types, in which SOCE is upregulated in G1/S transition and downregulated from S to G2/M transition. Pharmacological or siRNA inhibition of STIM1-Orai1 pathway of SOCE inhibits the phosphorylation of CDK2 and upregulates the expression of cyclin E, resulting in autophagy accompanied with cell cycle arrest in G1/S transition. The subsequently transient expression of STIM1 cDNA in STIM1-/- MEF rescues the phosphorylation and nuclear translocation of CDK2, suggesting that STIM1-mediated SOCE activation directly regulates CDK2 activity. Opposite to the important role of SOCE in controlling G1/S transition, the downregulated SOCE is a passive phenomenon from S to G2/M transition. This study uncovers SOCE-mediated Ca2+ microdomain that is the molecular basis for the Ca2+ sensitivity controlling G1/S transition.

Original languageEnglish
Article number22142
JournalScientific reports
Volume26
Issue number6
DOIs
Publication statusPublished - 2016 Feb 26

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G1 Phase Cell Cycle Checkpoints
Cell Cycle
Down-Regulation
Cell Membrane Structures
Phosphorylation
Cyclin E
Autophagy
Cell Cycle Checkpoints
Endoplasmic Reticulum
Small Interfering RNA
Up-Regulation
Complementary DNA
Pharmacology

All Science Journal Classification (ASJC) codes

  • General

Cite this

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abstract = "Ca2+ signaling is important to trigger the cell cycle progression, while it remains elusive in the regulatory mechanisms. Here we show that store-operated Ca2+ entry (SOCE), mediated by the interaction between STIM1 (an endoplasmic reticulum Ca2+ sensor) and Orai1 (a cell membrane pore structure), controls the specific checkpoint of cell cycle. The fluctuating SOCE activity during cell cycle progression is universal in different cell types, in which SOCE is upregulated in G1/S transition and downregulated from S to G2/M transition. Pharmacological or siRNA inhibition of STIM1-Orai1 pathway of SOCE inhibits the phosphorylation of CDK2 and upregulates the expression of cyclin E, resulting in autophagy accompanied with cell cycle arrest in G1/S transition. The subsequently transient expression of STIM1 cDNA in STIM1-/- MEF rescues the phosphorylation and nuclear translocation of CDK2, suggesting that STIM1-mediated SOCE activation directly regulates CDK2 activity. Opposite to the important role of SOCE in controlling G1/S transition, the downregulated SOCE is a passive phenomenon from S to G2/M transition. This study uncovers SOCE-mediated Ca2+ microdomain that is the molecular basis for the Ca2+ sensitivity controlling G1/S transition.",
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The STIM1-Orai1 pathway of store-operated Ca2+ entry controls the checkpoint in cell cycle G1/S transition. / Chen, Yun Wen; Chen, Yih Fung; Chen, Ying Ting; Chiu, Wen Tai; Shen, Meng Ru.

In: Scientific reports, Vol. 26, No. 6, 22142, 26.02.2016.

Research output: Contribution to journalArticle

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