Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Pancreatic Cancer (Jul 2025)
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
Reawakening the cellular death program in neoplasia through the therapeutic blockade of IAP function
Casey W. Wright, Colin S. Duckett
Casey W. Wright, Colin S. Duckett
Published October 3, 2005
Citation Information: J Clin Invest. 2005;115(10):2673-2678. https://doi.org/10.1172/JCI26251.
View: Text | PDF
Review Series

Reawakening the cellular death program in neoplasia through the therapeutic blockade of IAP function

  • Text
  • PDF
Abstract

Recent studies have shown that members of the inhibitor of apoptosis (IAP) protein family are highly expressed in several classes of cancer. The primary implication of these findings is that the elevated expression of IAPs is not coincidental but actually participates in oncogenesis by helping to allow the malignant cell to avoid apoptotic cell death. This concept, together with the discovery of several IAP-regulatory proteins that use a conserved mode of action, has stimulated a major effort by many research groups to devise IAP-targeting strategies as a means of developing novel antineoplastic drugs. In this Review, we consider the evidence both for and against the IAPs being valid therapeutic targets, and we describe the types of strategies being used to neutralize their functions.

Authors

Casey W. Wright, Colin S. Duckett

×

Figure 3

Options: View larger image (or click on image) Download as PowerPoint
Smac/DIABLO displaces caspase-9 from BIR3 of XIAP. (A) Crystal structure...
Smac/DIABLO displaces caspase-9 from BIR3 of XIAP. (A) Crystal structure of processed caspase-9 bound to BIR3 of XIAP. The purple peptide represents the first 4 amino acids that contact XIAP, with the amino terminus near the orange residue of XIAP. Coordinates were obtained from Brookhaven Protein Databank file 1NW9 (82). (B) NMR structure of the Smac/DIABLO IBM (purple peptide with the amino terminus near the orange residue of XIAP) bound to the same groove on BIR3 of XIAP that binds caspase-9, thus abrogating the ability of XIAP to block caspase-9 activity. Coordinates were obtained from Brookhaven Protein Databank file 1G3F (83). The 4 residues displayed in van der Waals radii spacefill on XIAP BIR3 are Gly306 (red), Leu307 (green), Trp310 (yellow), and Glu314 (orange). These 4 residues are critical in forming the Smac/DIABLO–binding groove on XIAP BIR3 (84). Images were created using Protein Explorer (85, 86).

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts