Oxysterol-binding Protein (OSBP)-related Protein 4 (ORP4) Is Essential for Cell Proliferation and Survival

• DOI: 10.1074/jbc.m114.571216
• Publication Date: 2014-04-18T06:23:39Z
• Authors: Mark Charman; Terry R. Colbourne; Antonietta Pietra...; Laurent Kreplak; Neale D. Ridgway
• Keywords: Pleckstrin homology domain

Oxysterol-binding protein (OSBP) and OSBP-related proteins (ORPs) comprise a large gene family with sterol/lipid transport regulatory activities. ORP4 (OSBP2) is closely related paralogue of OSBP, but its function unknown. Here we show that binds similar sterol lipid ligands as OSBP other ORPs uniquely required for the proliferation survival cultured cells. Recombinant ORP4L variant without pleckstrin homology (PH) domain (ORP4S) bind 25-hydroxycholesterol extract transfer cholesterol between liposomes. Two conserved histidine residues in are essential binding phosphatidylinositol 4-phosphate not sterols. The PH also Golgi apparatus. However, context ORP4L, normal organization vimentin network. Unlike RNAi silencing all variants (including partial truncation termed ORP4M) HEK293 HeLa cells resulted growth arrest cell death. non-transformed intestinal epithelial (IEC)-18 caused apoptosis characterized by caspase 3 poly(ADP-ribose) polymerase processing, DNA cleavage, JNK phosphorylation. IEC-18 transformed oncogenic H-Ras have increased expression ORP4S resistant to growth-inhibitory effects silencing. Results suggest promotes rapidly proliferating