Aug 31, 2019

The effect of the chemical chaperone 4-phenylbutyrate on secretion and activity of the p.Q160R missense variant of coagulation factor FVII

Cell & Bioscience
Elisabeth AndersenGrethe Skretting


Congenital coagulation factor (F) VII deficiency is a rare bleeding disorder caused by mutations in the F7 gene. The missense factor FVII variant p.Q160R is the disease-causing mutation in all Norwegian FVII deficient patients and results in reduced biological activity and antigen levels of FVII in patient plasma. Previous in vitro studies on this variant demonstrated impaired intracellular trafficking and reduced secretion, possibly due to protein misfolding. The aim of the study was therefore to assess the impact of chemical chaperones on cellular processing and secretion of this variant using a cell model based on overexpression of the recombinant protein. Through screening of compounds, we identified 4-phenylbutyrate (4-PBA) to increase the secretion of recombinant (r) FVII-160R by ~ 2.5-fold. Additionally, treatment with 4-PBA resulted in a modest increase in specific biological activity. Intracellular localization studies revealed that upon treatment with 4-PBA, rFVII-160R was secreted through Golgi and Golgi reassembly-stacking protein (GRASP)-structures. The present study demonstrates that the chemical chaperone 4-PBA, restores intracellular trafficking and increases the secretion of a missense FVII variant with functio...Continue Reading

  • References
  • Citations


  • We're still populating references for this paper, please check back later.
  • References
  • Citations


  • This paper may not have been cited yet.

Mentioned in this Paper

Benzeneboronic acid
Cavity of Golgi Vesicle
Cellular Process
Golgi Reassembly
Viral Structural Proteins
In Vitro Study
F7 gene

Trending Feeds


Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Bone Marrow Neoplasms

Bone Marrow Neoplasms are cancers that occur in the bone marrow. Discover the latest research on Bone Marrow Neoplasms here.

IGA Glomerulonephritis

IgA glomerulonephritis is a chronic form of glomerulonephritis characterized by deposits of predominantly Iimmunoglobin A in the mesangial area. Discover the latest research on IgA glomerulonephritis here.

Cryogenic Electron Microscopy

Cryogenic electron microscopy (Cryo-EM) allows the determination of biological macromolecules and their assemblies at a near-atomic resolution. Here is the latest research.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

LRRK2 & Immunity During Infection

Mutations in the LRRK2 gene are a risk-factor for developing Parkinson’s disease. However, LRRK2 has been shown to function as a central regulator of vesicular trafficking, infection, immunity, and inflammation. Here is the latest research on the role of this kinase on immunity during infection.

Antiphospholipid Syndrome

Antiphospholipid syndrome or antiphospholipid antibody syndrome (APS or APLS), is an autoimmune, hypercoagulable state caused by the presence of antibodies directed against phospholipids.

Meningococcal Myelitis

Meningococcal myelitis is characterized by inflammation and myelin damage to the meninges and spinal cord. Discover the latest research on meningococcal myelitis here.

Alzheimer's Disease: MS4A

Variants within membrane-spanning 4-domains subfamily A (MS4A) gene cluster have recently been implicated in Alzheimer's disease by recent genome-wide association studies. Here is the latest research.