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Cannabinoid receptor activation inhibits cell cycle progression by modulating 14-3-3β
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Cannabinoid receptor activation inhibits cell cycle progression by modulating 14-3-3β
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Cannabinoid receptor activation inhibits cell cycle progression by modulating 14-3-3β
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Journal Article
Cannabinoid receptor activation inhibits cell cycle progression by modulating 14-3-3β
2014
Overview
Cannabinoids display various pharmacological activities, including tumor regression, anti-inflammatory and neuroprotective effects. To investigate the molecular mechanisms underlying the pharmacological effects of cannabinoids, we used a yeast two-hybrid system to screen a mouse brain cDNA library for proteins interacting with type 1 cannabinoid receptor (CB1R). Using the intracellular loop 3 of CB1R as bait, we identified 14-3-3β as an interacting partner of CB1R and confirmed their interaction using affinity-binding assays. 14-3-3β has been reported to induce a cell cycle delay at the G
2
/M phase. We tested the effects of cannabinoids on cell cycle progression in HeLa cells synchronized using a double-thymidine block-and-release protocol and found an increase in the population of G
2
/M phase cells. We further found that CB1R activation augmented the interaction of 14-3-3β with Wee1 and Cdc25B, and promoted phosphorylation of Cdc2 at Tyr-15. These results suggest that cannabinoids induce cell cycle delay at the G2/M phase by activating 14-3-3β.
Publisher
Versita
Subject
/ 14-3-3 Proteins - metabolism
/ Animals
/ Biological and Medical Physics
/ Biomedical and Life Sciences
/ Cdc2
/ Cdc25B
/ Cell Division - drug effects
/ Cyclin B
/ G2 Phase Cell Cycle Checkpoints - drug effects
/ G2 Phase Cell Cycle Checkpoints - genetics
/ G2 Phase Cell Cycle Checkpoints - physiology
/ GIPs
/ HeLa
/ Humans
/ Mice
/ Receptor, Cannabinoid, CB1 - genetics
/ Receptor, Cannabinoid, CB1 - metabolism
/ Signal Transduction - drug effects
/ Signal Transduction - genetics
/ Signal Transduction - physiology
/ Two-Hybrid System Techniques
/ Wee1
