Open Access

Cannabinoid receptor activation inhibits cell cycle progression by modulating 14-3-3β

Cellular & Molecular Biology LettersAn International Journal201419:200

https://doi.org/10.2478/s11658-014-0200-x

Received: 10 December 2013

Accepted: 1 July 2014

Published: 7 July 2014

Abstract

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 G2/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 G2/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.

Keywords

Cannabinoids Cdc2 Cdc25B Cyclin B G2/M phase GIPs HeLa Phosphorylation Wee1 Yeast-two hybrid

Notes

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