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Determination of the Relative Potency of an Anti-TNF Monoclonal Antibody (mAb) by Neutralizing TNF Using an In Vitro Bioanalytical Method
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EVER2 protein binds TRADD to promote TNF-α-induced apoptosis

G Gaud1, D Guillemot, Y Jacob

  • 1Unité de Génétique, Papillomavirus et Cancer Humain, Institut Pasteur, Paris, France.

Cell Death & Disease
|February 23, 2013
PubMed

Insights

EVER2 protein plays a crucial role in skin cancer prevention by inducing cell death. Its interaction with TRADD is vital for this function, and defects are linked to increased cancer risk.

Area of Science:

  • Molecular Biology
  • Immunology
  • Dermatology

Background:

  • EVER1 and EVER2 proteins regulate human papillomavirus (HPV) infections by modulating the AP-1 signaling pathway.
  • Defects in EVER expression are linked to epidermodysplasia verruciformis, characterized by persistent HPV infection, TNF-α overproduction, and skin cancer development.

Purpose of the Study:

  • To investigate the role of EVER proteins in TNF-α-induced apoptosis, a key cellular defense mechanism against viral persistence.
  • To elucidate the function of EVER2 in cell death pathways triggered by extrinsic stimuli.

Main Methods:

  • Investigated EVER2's interaction with TRADD, TRAF2, and RIPK1.
  • Analyzed the effect of EVER2 on TNF-α and TRAIL-induced apoptosis.
  • Examined the functional consequences of the skin cancer-associated EVER2 I306 allele on TRADD interaction and cell death.

Main Results:

  • EVER2 was shown to induce TNF-α- and TRAIL-dependent apoptosis.
  • EVER2 interacts with the N-terminal domain of TRADD, hindering the recruitment of TRAF2 and RIPK1, thereby promoting apoptosis.
  • The EVER2 I306 allele impairs TRADD-EVER2 interaction, leading to reduced cell death upon TNF-α treatment.

Conclusions:

  • EVER2 possesses a critical function in controlling cell survival by mediating apoptosis in response to death stimuli.
  • This finding reveals a novel mechanism by which EVER2 contributes to skin cancer prevention.
  • Dysfunctional EVER2-TRADD interaction is implicated in increased susceptibility to skin cancer.

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