Δ9-Tetrahydrocannabinol regulates the p53 post-translational modifiers Murine double minute 2 and the Small Ubiquitin MOdifier protein in the rat brain

The phytocannabinoid Δ9-Tetrahydrocannabinol (Δ9-THC), the main psychoactive cannabinoid in cannabis, activates a number of signalling cascades including p53. This study examines the role of Δ9-THC in regulating the p53 post-translational modifier proteins, Murine double minute (Mdm2) and Small Ubquitin-like MOdifier protein 1 (SUMO-1) in cortical neurons. Δ9-THC increased both Mdm2 and SUMO-1 protein expression and induced the deSUMOylation of p53 in a cannabinoid receptor type 1 (CB1)-receptor dependent manner. We demonstrate that Δ9-THC decreased the SUMOylation of the CB1 receptor. The data reveal a novel role for cannabinoid receptor activation in modulating the SUMO regulatory system.Structured summaryMINT-7266621: Cb1 (uniprotkb:P20272) physically interacts (MI:0915) with SUMO-1 (uniprotkb:Q5I0H3) by anti bait coimmunoprecipitation(MI:0006)MINT-7266633: SUMO-1 (uniprotkb:Q5I0H3) and Cb1 (uniprotkb:P20272) colocalize (MI:0403) by fluorescence microscopy (MI:0416)MINT-7266611: p53 (uniprotkb:P10361) physically interacts (MI:0915) with SUMO-1 (uniprotkb:Q5I0H3) by anti bait coimmunoprecipitation (MI:0006)