The protein phosphatase 2A represents a novel cellular target for hepatitis C virus NS5A protein

Urania Georgopoulou1, Panagiota Tsitoura, Maria Kalamvoki

  • 1Molecular Virology Laboratory, Hellenic Pasteur Institute, 127, Vas. Sofias Avenue, Athens 11521, Greece. uraniag@mail.pasteur.gr

Biochimie
|February 8, 2006
PubMed

Insights

Hepatitis C virus NS5A protein stimulates phosphatase 2A (PP2A) activity in cells. This viral protein interacts with PP2A subunits, suggesting NS5A is a novel PP2A regulatory protein impacting cell growth.

Area of Science:

  • Virology
  • Cell Biology
  • Molecular Biology

Background:

  • Hepatitis C virus (HCV) NS5A protein is known to affect the extracellular signal-regulated kinase (ERK) pathway.
  • Protein phosphatase 2A (PP2A) regulates cell signaling pathways, including the Ras-Raf mitogen-activated protein (MAP) kinase pathway.

Purpose of the Study:

  • To investigate the interaction between HCV NS5A protein and PP2A.
  • To determine if NS5A influences PP2A activity in vivo.
  • To explore the potential role of NS5A as a regulator of PP2A.

Main Methods:

  • Transient expression of full-length HCV NS5A protein in various cell lines.
  • Measurement of PP2A activity in cells, with and without okadaic acid (a PP2A inhibitor).
  • In vivo and in vitro co-immunoprecipitation assays to detect interactions between NS5A and PP2A subunits (A and C).

Main Results:

  • HCV NS5A expression significantly increased PP2A activity in living cells.
  • The enhanced PP2A activity was specifically inhibited by okadaic acid.
  • NS5A protein was found to interact with both the scaffolding A and catalytic C subunits of PP2A.

Conclusions:

  • HCV NS5A protein acts as a novel viral regulator of PP2A activity.
  • NS5A's interaction with PP2A subunits suggests a mechanism for deregulating host cell signaling.
  • This interaction may play a crucial role in HCV's ability to control host cell growth and survival.

Related Concept Videos

Hepatitis01:25

Hepatitis

Hepatitis is an inflammatory condition of the liver most commonly caused by hepatotropic viruses (A–E), though non-infectious causes such as alcohol and drugs also exist.Hepatitis AHepatitis A virus (HAV) is a non-enveloped RNA virus of the Picornaviridae family. It is primarily transmitted via the fecal-oral route, typically through ingestion of contaminated food or water. After ingestion, HAV enters the bloodstream through the oropharynx or intestinal epithelium and reaches the liver. The...
Protein Kinases and Phosphatases02:54

Protein Kinases and Phosphatases

Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
Protein Kinases and Phosphatases02:54

Protein Kinases and Phosphatases

Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
Inhibitors of Viral Protein Synthesis01:30

Inhibitors of Viral Protein Synthesis

Protein synthesis is indispensable for viral replication, as viruses lack the cellular machinery required for this process and must hijack the host's translational apparatus. In response, host cells deploy a critical innate immune defense involving interferons, specialized cytokines that play a central role in inhibiting viral propagation.Upon viral detection, infected cells release interferons that bind to receptors on adjacent uninfected cells, activating the JAK-STAT signaling pathway and...
Transducer Mechanism: Enzyme-Linked Receptors01:27

Transducer Mechanism: Enzyme-Linked Receptors

Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:
Phosphorylation01:02

Phosphorylation

The addition or removal of phosphate groups from proteins is the most common chemical modification that regulates cellular processes. These modifications can affect the structure, activity, stability, and localization of proteins within cells as well as their interactions with other proteins.
During phosphorylation, protein kinases transfer the terminal phosphate group of ATP to specific amino acid side chains of substrate proteins. Serine, threonine, and tyrosine are the most commonly...