TAT-RasGAP_317-326 kills cells by targeting inner-leaflet-enriched phospholipids.

ABSTRACT: TAT-RasGAP_317-326 is a cell-penetrating peptide-based construct with anticancer and antimicrobial activities. This peptide kills a subset of cancer cells in a manner that does not involve known programmed cell death pathways. Here we have elucidated the mode of action allowing TAT-RasGAP_317-326 to kill cells. This peptide binds and disrupts artificial membranes containing lipids typically enriched in the inner leaflet of the plasma membrane, such as phosphatidylinositol-bisphosphate (PIP₂) and phosphatidylserine (PS). Decreasing the amounts of PIP₂ in cells renders them more resistant to TAT-RasGAP_317-326, while reducing the ability of cells to repair their plasma membrane makes them more sensitive to the peptide. The W317A TAT-RasGAP<

SUBMITTER: Serulla M 

PROVIDER: S-EPMC7749316 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature