Related Experiment Video

Updated: Jul 12, 2026

Development and Validation of an Ultrasensitive Single Molecule Array Digital Enzyme-linked Immunosorbent Assay for Human Interferon-α
08:26

Development and Validation of an Ultrasensitive Single Molecule Array Digital Enzyme-linked Immunosorbent Assay for Human Interferon-α

Published on: June 14, 2018

Antiproliferative activity of the human IFN-alpha-inducible protein IFI44

L C Hallen1, Y Burki, M Ebeling

  • 1Roche Center for Medical Genomics, F. Hoffmann-La Roche Ltd., 4070 Basel, Switzerland.

Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research
|September 6, 2007
PubMed

Insights

The interferon-alpha-inducible protein IFI44, linked to hepatitis C virus (HCV), halts cell growth by binding GTP and disrupting ERK signaling. This antiviral mechanism functions independently of interferon-alpha response.

Area of Science:

  • Cell Biology
  • Virology
  • Molecular Biology

Background:

  • The interferon-alpha (IFN-alpha)-inducible protein IFI44 is associated with hepatitis C virus (HCV) infection, but its precise function remains unknown.
  • Understanding IFI44's role is crucial for deciphering host-pathogen interactions and potential therapeutic targets in viral infections.

Purpose of the Study:

  • To elucidate the cellular localization, expression kinetics, and functional role of the interferon-alpha-inducible protein IFI44.
  • To investigate the mechanism by which IFI44 influences cell proliferation and signaling pathways.

Main Methods:

  • Utilized human melanoma cell lines (ME15 and D10) for experimental analysis.
  • Employed immunofluorescence, viral overexpression, cellular fractionation, and molecular assays to study IFI44.
  • Investigated GTP binding capabilities and effects on extracellular signal-regulated kinase (ERK) signaling.

Main Results:

  • IFI44 transcription and protein expression were characterized following induction, with peak protein levels at 24 hours.
  • IFI44 was localized to the cytoplasm and demonstrated an antiproliferative effect in vitro, independent of IFN-alpha responsiveness.
  • IFI44 possesses a GTP binding site, and its overexpression led to GTP depletion, subsequent abolition of ERK signaling, and cell cycle arrest.

Conclusions:

  • IFI44 functions as a cytoplasmic protein that induces an antiproliferative state by sequestering intracellular GTP.
  • This GTP depletion disrupts ERK signaling, leading to cell cycle arrest, suggesting a novel antiviral mechanism.
  • The findings propose a model where IFI44 acts as a host-intrinsic defense factor against viral infections like HCV.

More Related Videos

High-throughput Quantitative Real-time RT-PCR Assay for Determining Expression Profiles of Types I and III Interferon Subtypes10:00

High-throughput Quantitative Real-time RT-PCR Assay for Determining Expression Profiles of Types I and III Interferon Subtypes

Published on: March 24, 2015

Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo08:19

Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo

Published on: July 20, 2019

Related Concept Videos

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...
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...