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References (1)

Title : APT2 Inhibition Restores Scribble Localization and S-Palmitoylation in Snail-Transformed Cells - Hernandez_2017_Cell.Chem.Biol_24_87
Author(s) : Hernandez JL , Davda D , Cheung See Kit M , Majmudar JD , Won SJ , Gang M , Pasupuleti SC , Choi AI , Bartkowiak CM , Martin BR
Ref : Cell Chemical Biology , 24 :87 , 2017
Abstract : The multidomain scaffolding protein Scribble (Scrib) organizes key signaling complexes to specify basolateral cell polarity and suppress aberrant growth. In many human cancers, genetically normal Scrib mislocalizes from cell-cell junctions to the cytosol, correlating with enhanced growth signaling and malignancy. Here we confirm that expression of the epithelial-to-mesenchymal transcription factor (EMT-TF) Snail in benign epithelial cells leads to Scrib displacement from the plasma membrane, mimicking the mislocalization observed in aggressive cancers. Upon further examination, Snail promotes a transcriptional program that targets genes in the palmitoylation cycle, repressing many protein acyl transferases and elevating expression and activity of protein acyl thioesterase 2 (APT2). APT2 isoform-selective inhibition or knockdown rescued Scrib membrane localization and palmitoylation while attenuating MEK activation. Overall, inhibiting APT2 restores balance to the Scrib palmitoylation cycle, promoting membrane re-localization and growth attenuation. These findings emphasize the importance of S-palmitoylation as a post-translational gatekeeper of cell polarity-mediated tumor suppression.
ESTHER : Hernandez_2017_Cell.Chem.Biol_24_87
PubMedSearch : Hernandez_2017_Cell.Chem.Biol_24_87
PubMedID: 28065656