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Baculovirus-based genetic screen for antiapoptotic genes identifies a novel IAP

S Seshagiri1, D Vucic, J Lee

  • 1Departments of Molecular Oncology, Genentech Inc., South San Francisco, California 94080, USA.

The Journal of Biological Chemistry
|December 14, 1999
PubMed

Insights

Researchers identified Tn-IAP1, a novel inhibitor of apoptosis, using a baculovirus genetic screen. This discovery aids in finding new cell death inhibitors for various applications.

Area of Science:

  • Molecular Biology
  • Virology
  • Cell Biology

Background:

  • Autographa californica multiple nuclear polyhedrosis virus (AcMNPV) utilizes the p35 gene to inhibit host cell apoptosis, crucial for viral propagation.
  • AcMNPV lacking the p35 gene induces apoptosis in infected insect cells, providing a tool for genetic screening.

Purpose of the Study:

  • To identify novel genes encoding inhibitors of apoptosis (IAPs) using a pro-apoptotic p35-null AcMNPV.
  • To characterize the function of newly identified IAPs in blocking programmed cell death.

Main Methods:

  • A genetic screen employing a p35-null AcMNPV was used to identify genes that rescue Sf-21 cells from apoptosis.
  • The identified gene, Tn-IAP1, was characterized for its ability to inhibit cell death induced by various stimuli.

Main Results:

  • The novel IAP family member, Tn-IAP1, was identified through the genetic screen.
  • Tn-IAP1 demonstrated the ability to block apoptosis induced by p35-null AcMNPV, actinomycin D, and Drosophila cell-death inducers (HID and GRIM).

Conclusions:

  • Tn-IAP1 is a functional inhibitor of apoptosis with conserved activity across different death pathways.
  • The developed genetic screening method using p35-null baculovirus is effective for discovering novel apoptosis inhibitors from diverse sources.

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