Analysis of candidate antagonists of IAP-mediated caspase inhibition using yeast reconstituted with the mammalian Apaf-1-activated apoptosis mechanism.

Journal Article (Journal Article)

We have reconstituted the Apaf-1-activated apoptosis mechanism in Sacchromyces cerevisiae such that the presence of a constitutively active form of Apaf-1 together with both Caspase-9 and Caspase-3 results in yeast death. This system is a good model of the Apaf-1-activated pathway in mammalian cells: MIHA (XIAP/hILP), and to a lesser degree MIHB (c-IAP1/HIAP2) and MIHC (c-IAP-2/HIAP1) can inhibit caspases in this system, and protection by IAPs (inhibitor of apoptosis) can be abrogated by coexpression of the Drosophila pro-apoptotic proteins HID and GRIM or the mammalian protein DIABLO/Smac. Using this system we demonstrate that unlike DIABLO/Smac, other proteins which interact with mammalian IAPs (TAB-1, Zap-1, Traf-1 and Traf-2) do not act to antagonise IAP- mediated caspase inhibition.

Full Text

Duke Authors

Cited Authors

  • Hawkins, CJ; Silke, J; Verhagen, AM; Foster, R; Ekert, PG; Ashley, DM

Published Date

  • October 1, 2001

Published In

Volume / Issue

  • 6 / 5

Start / End Page

  • 331 - 338

PubMed ID

  • 11483856

International Standard Serial Number (ISSN)

  • 1360-8185

Digital Object Identifier (DOI)

  • 10.1023/a:1011329917895


  • eng

Conference Location

  • Netherlands