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AIFsh, a novel apoptosis-inducing factor (AIF) pro-apoptotic isoform with potential pathological relevance in human

Cécile Delettre1, Victor J Yuste, Rana S Moubarak

  • 1Apoptose et Système Immunitaire, CNRS-URA 1961 and Plateforme 5-Production de Protéines Recombinantes et d'Anticorps, Institut Pasteur, 25, rue du Dr. Roux, 75015 Paris, France.

The Journal of Biological Chemistry
|December 21, 2005
PubMed

Insights

Researchers discovered a new AIF isoform, AIFshort (AIFsh), which triggers caspase-independent cell death. This isoform

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Genetics

Background:

  • Apoptosis-inducing Factor (AIF) is a key mediator of caspase-independent cell death.
  • AIF is encoded by a single gene on the X chromosome.
  • Two AIF isoforms, AIF and AIF-exB, were previously identified.

Purpose of the Study:

  • To identify novel isoforms of AIF.
  • To investigate the role of a newly discovered AIF isoform in cell death and cancer.

Main Methods:

  • Identification of a novel AIF isoform (AIFsh) using an alternate transcriptional start site.
  • Overexpression of AIFsh in HeLa cells.
  • Analysis of AIFsh effects on nuclear translocation, chromatin condensation, and DNA fragmentation.
  • Assessment of AIFsh regulation in various tumor cells and after gamma-irradiation.

Main Results:

  • A third AIF isoform, AIFshort (AIFsh), was identified, comprising the C-terminal domain (amino acids 353-613).
  • AIFsh overexpression induces nuclear translocation and caspase-independent cell death, including chromatin condensation and DNA fragmentation.
  • The N-terminal 352 amino acids of AIF are not essential for its apoptotic activity.
  • AIFsh is downregulated in multiple tumor types but upregulated by gamma irradiation.

Conclusions:

  • AIFsh is a novel pro-apoptotic AIF isoform.
  • The apoptotic function of AIF does not require its N-terminal domain.
  • AIFsh plays a role in tumor suppression and its dysregulation is implicated in cancer formation.

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