Delta(9)-tetrahydrocannabinol regulates the p53 post-translational modifiers Murine double minute 2 and the Small Ubiquitin MOdifier protein in the rat brain.
The phytocannabinoid Delta(9)-Tetrahydrocannabinol (Delta(9)-THC), the main psychoactive cannabinoid in cannabis, activates a number of signalling cascades including p53. This study examines the role of Delta(9)-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. Delta(9)-THC increased both Mdm2 and SUMO-1 protein expression and induced the deSUMOylation of p53 in a cannabinoid receptor type 1 (CB(1))-receptor dependent manner. We demonstrate that Delta(9)-THC decreased the SUMOylation of the CB(1) receptor. The data reveal a novel role for cannabinoid receptor activation in modulating the SUMO regulatory system.
Gowran
Aoife
A
Department of Physiology, Trinity College Institute of Neuroscience, Trinity College, Dublin 2, Ireland. gowrana@tcd.ie
Murphy
Carrie E
CE
Campbell
Veronica A
VA
D000818:Animals; D001921:Brain / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D013759:Dronabinol / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000187:drug effects*; D051736:Proto-Oncogene Proteins c-mdm2 / Q000378:metabolism*; D051381:Rats; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism; D025842:SUMO-1 Protein / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D043884:Receptor, Cannabinoid, CB1; D025842:SUMO-1 Protein; D016159:Tumor Suppressor Protein p53; D013759:Dronabinol; D051736:Proto-Oncogene Proteins c-mdm2