APT2 Inhibition Restores Scribble Localization and S-Palmitoylation in Snail-Transformed Cells.
Cell Chem Biol
; 24(1): 87-97, 2017 Jan 19.
Article
en En
| MEDLINE
| ID: mdl-28065656
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Tioléster Hidrolasas
/
Proteínas Supresoras de Tumor
/
Células Epiteliales
/
Transición Epitelial-Mesenquimal
/
Factores de Transcripción de la Familia Snail
/
Proteínas de la Membrana
Límite:
Humans
Idioma:
En
Revista:
Cell Chem Biol
Año:
2017
Tipo del documento:
Article
País de afiliación:
Estados Unidos