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Publication : ZDHHC7-mediated S-palmitoylation of Scribble regulates cell polarity.

First Author  Chen B Year  2016
Journal  Nat Chem Biol Volume  12
Issue  9 Pages  686-93
PubMed ID  27380321 Mgi Jnum  J:285024
Mgi Id  MGI:6393185 Doi  10.1038/nchembio.2119
Citation  Chen B, et al. (2016) ZDHHC7-mediated S-palmitoylation of Scribble regulates cell polarity. Nat Chem Biol 12(9):686-93
abstractText  Scribble (SCRIB) is a tumor-suppressor protein, playing critical roles in establishing and maintaining epithelial cell polarity. SCRIB is frequently amplified in human cancers but does not localize properly to cell-cell junctions, suggesting that mislocalization of SCRIB disrupts its tumor-suppressive activities. Using chemical reporters, here we showed that SCRIB localization was regulated by S-palmitoylation at conserved cysteine residues. Palmitoylation-deficient mutants of SCRIB were mislocalized, leading to disruption of cell polarity and loss of their tumor-suppressive activities to oncogenic YAP, MAPK and PI3K/AKT pathways. We further found that ZDHHC7 was the major palmitoyl acyltransferase regulating SCRIB. Knockout of ZDHHC7 led to SCRIB mislocalization and YAP activation, and disruption of SCRIB's suppressive activities in HRas(V12)-induced cell invasion. In summary, we demonstrated that ZDHHC7-mediated SCRIB palmitoylation is critical for SCRIB membrane targeting, cell polarity and tumor suppression, providing new mechanistic insights of how dynamic protein palmitoylation regulates cell polarity and tumorigenesis.
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