Delta(9)-tetrahydrocannabinol regulates the p53 post-translational modifiers Murine double minute 2 and the Small Ubiquitin MOdifier protein in the rat brain

FEBS Lett. 2009 Nov 3;583(21):3412-8. doi: 10.1016/j.febslet.2009.09.056. Epub 2009 Oct 9.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / cytology
  • Brain / drug effects*
  • Brain / metabolism*
  • Dronabinol / pharmacology*
  • Gene Expression Regulation / drug effects
  • Mice
  • Neurons / drug effects
  • Neurons / metabolism
  • Protein Processing, Post-Translational / drug effects*
  • Proto-Oncogene Proteins c-mdm2 / metabolism*
  • Rats
  • Receptor, Cannabinoid, CB1 / metabolism
  • SUMO-1 Protein / metabolism*
  • Tumor Suppressor Protein p53 / metabolism*


  • Receptor, Cannabinoid, CB1
  • SUMO-1 Protein
  • Tumor Suppressor Protein p53
  • Dronabinol
  • Proto-Oncogene Proteins c-mdm2