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

Aoife Gowran, Carrie E. Murphy, Veronica A. Campbell

Research output: Contribution to journalArticle

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).

Original languageEnglish
Pages (from-to)3412-3418
Number of pages7
JournalFEBS Letters
Volume583
Issue number21
DOIs
Publication statusPublished - Nov 3 2009

Keywords

  • Δ-Tetrahydrocannabinol
  • Cannabinoid
  • Murine double minute
  • Post-translational modification
  • Signal transduction
  • Small Ubquitin-like MOdifier

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Genetics
  • Molecular Biology
  • Structural Biology

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