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

Abstract 

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 summary

MINT-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)

Keywords: Cannabinoid, Δ⁹-Tetrahydrocannabinol, Murine double minute, Small Ubquitin-like MOdifier, Post-translational modification, Signal transduction

Abbreviations: Δ⁹-THC, Δ⁹-Tetrahydrocannabinol, CB₁, the cannabinoid receptor type 1, Mdm2, Murine double minute 2, SUMO-1, Small Ubquitin MOdifier protein 1, Ψ, large hydrophobic residue, K, lysine, X, any amino acid, E, glutamic acid, HRP, horse radish peroxidase, WB, Western immunoblot, IP, immunoprecipitation