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

研究成果: Article査読

41 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)1467-1480
ページ数14
ジャーナルJournal of Cell Biology
179
7
DOI
出版ステータスPublished - 2007 12 31
外部発表はい

ASJC Scopus subject areas

  • 細胞生物学

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