The Phosphofurin Acidic Cluster Sorting Protein 2 (PACS-2) E209K Mutation Responsible for PACS-2 Syndrome Increases Susceptibility to Apoptosis.

ABSTRACT: Phosphofurin acidic cluster sorting protein 2 (PACS-2) is a multifunctional cytosolic membrane trafficking protein with distinct roles in maintaining cellular homeostasis. Recent clinical reports have described 28 individuals possessing a de novo PACS-2 E209K mutation that present with epileptic seizures and cerebellar dysgenesis. As the PACS-2 E209K missense mutation has become a marker for neurodevelopmental disorders, we sought to characterize its biochemical properties. Accordingly, we observed that the PACS-2 E209K protein exhibited a slower turnover rate relative to PACS-2 wild type (WT) upon cycloheximide treatment in 293T cells. The longer half-life of PACS-2 E209K suggests a disruption in its proteostasis, with the potential for altered protein-protein interactions. Indeed,

SUBMITTER: Zang RX 

PROVIDER: S-EPMC9520720 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature