DIAP2 functions as a mechanism-based regulator of drICE that contributes to the caspase activity threshold in living cells

Paulo S. Ribeiro, Erina Kuranaga, Tencho Tenev, François Leulier, Masayuki Miura, Pascal Meier

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

In addition to their well-known function in apoptosis, caspases are also important in several nonapoptotic processes. How caspase activity is restrained and shut down under such nonapoptotic conditions remains unknown. Here, we show that Drosophila melanogaster inhibitor of apoptosis protein 2 (DIAP2) controls the level of caspase activity in living cells. Animals that lack DIAP2 have higher levels of drICE activity. Although diap2-deficient cells remain viable, they are sensitized to apoptosis following treatment with sublethal doses of x-ray irradiation. We find that DIAP2 regulates the effector caspase drICE through a mechanism that resembles the one of the caspase inhibitor p35. As for p35, cleavage of DIAP2 is required for caspase inhibition. Our data suggest that DIAP2 forms a covalent adduct with the catalytic machinery of drICE. In addition, DIAP2 also requires a functional RING finger domain to block cell death and target drICE for ubiquitylation. Because DIAP2 efficiently interacts with drICE, our data suggest that DIAP2 controls drICE in its apoptotic and nonapoptotic roles.

Original languageEnglish
Pages (from-to)1467-1480
Number of pages14
JournalJournal of Cell Biology
Volume179
Issue number7
DOIs
Publication statusPublished - 2007 Dec 31

ASJC Scopus subject areas

  • Cell Biology

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