Related Experiment Video

Updated: May 1, 2026

Fluorescence-Based Measurements of Phosphatidylserine/Phosphatidylinositol 4-Phosphate Exchange Between Membranes
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Fluorescence-Based Measurements of Phosphatidylserine/Phosphatidylinositol 4-Phosphate Exchange Between Membranes

Published on: March 14, 2021

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Oxysterol-binding protein (OSBP)-related protein 4 (ORP4) is essential for cell proliferation and survival

Mark Charman1, Terry R Colbourne1, Antonietta Pietrangelo1

  • 1From the Departments of Pediatrics, Biochemistry and Molecular Biology, and.

The Journal of Biological Chemistry
|April 19, 2014
PubMed

Insights

Oxysterol-binding protein 4 (ORP4) is crucial for cell proliferation and survival, binding lipids and regulating cell growth. Its absence causes growth arrest or apoptosis, highlighting its role in maintaining cellular integrity.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Lipid Metabolism

Background:

  • Oxysterol-binding protein (OSBP) and OSBP-related proteins (ORPs) are key players in sterol/lipid transport.
  • The function of ORP4 (OSBP2), a paralogue of OSBP, remained largely unknown.
  • This study investigates the specific role of ORP4 in cellular processes.

Purpose of the Study:

  • To elucidate the function of ORP4 in cell proliferation and survival.
  • To characterize the ligand-binding properties and cellular localization of ORP4.
  • To determine the impact of ORP4 deficiency on different cell types.

Main Methods:

  • Recombinant protein expression and lipid-binding assays.
  • RNA interference (RNAi) to silence ORP4 variants in various cell lines (HEK293, HeLa, IEC-18).
  • Analysis of cell proliferation, apoptosis markers (caspase 3, PARP), DNA cleavage, and protein phosphorylation (JNK).

Main Results:

  • ORP4 binds sterols and lipids, including 25-hydroxycholesterol, and transfers cholesterol between liposomes.
  • Specific histidine residues in ORP4 are essential for phosphatidylinositol 4-phosphate binding.
  • ORP4 silencing leads to growth arrest in cancer cell lines but apoptosis in non-transformed intestinal epithelial cells.
  • Oncogenic H-Ras transformation confers resistance to ORP4 silencing-induced growth inhibition.

Conclusions:

  • ORP4 plays a unique and essential role in promoting the proliferation and survival of cultured cells.
  • The PH domain of ORP4 is involved in phosphatidylinositol 4-phosphate binding and vimentin network organization.
  • ORP4 is critical for the survival of rapidly proliferating cells, and its dysregulation is linked to cancer cell resistance.
Keywords:
ApoptosisCholesterolLipid TransportOxysterol-binding ProteinPhosphatidylinositol 4-PhosphatePhospholipidRNA Interference (RNAi)Vimentin

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