title: Cannabinoid receptor activation inhibits cell cycle progression by modulating 14-3-3β.
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.
authors.affiliation: Department of Life Science, Kyonggi University, Suwon, 443-760, Republic of Korea.
authors.forename: Hye-Won
authors.initials: HW
authors.lastname: Jung
authors.forename: Inae
authors.initials: I
authors.lastname: Park
authors.forename: Sungho
authors.initials: S
authors.lastname: Ghil
mesh_terms: D048948:14-3-3 Proteins / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002186:Cannabinoids / Q000494:pharmacology; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology*; D002455:Cell Division / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D005434:Flow Cytometry; D016195:G2 Phase / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D015151:Immunoblotting; D051379:Mice; D011485:Protein Binding; D043884:Receptor, Cannabinoid, CB1 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D020798:Two-Hybrid System Techniques
chemical_list: D048948:14-3-3 Proteins; D002186:Cannabinoids; D043884:Receptor, Cannabinoid, CB1