Hernandez_2017_Cell.Chem.Biol_24_87

Reference

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

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Citations formats

Hernandez JL, Davda D, Cheung See Kit M, Majmudar JD, Won SJ, Gang M, Pasupuleti SC, Choi AI, Bartkowiak CM, Martin BR (2017)
APT2 Inhibition Restores Scribble Localization and S-Palmitoylation in Snail-Transformed Cells
Cell Chemical Biology 24 :87

Hernandez JL, Davda D, Cheung See Kit M, Majmudar JD, Won SJ, Gang M, Pasupuleti SC, Choi AI, Bartkowiak CM, Martin BR (2017)
Cell Chemical Biology 24 :87

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    [paper] => Hernandez_2017_Cell.Chem.Biol_24_87
    [author] => Hernandez JL || Davda D || Cheung See Kit M || Majmudar JD || Won SJ || Gang M || Pasupuleti SC || Choi AI || Bartkowiak CM || Martin BR
    [year] => 2017
    [title] => APT2 Inhibition Restores Scribble Localization and S-Palmitoylation in Snail-Transformed Cells
    [journal] => Cell Chemical Biology
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    [page] => 87
    [medline] => 28065656
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            [content] => 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.
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