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Drosophila Bruce Can Potently Suppress Rpr- and Grim-Dependent but Not Hid-Dependent Cell Death

Vernooy, Stephanie Y. and Chow, Vivian and Su, Julius and Verbrugghe, Koen and Yang, Jennifer and Cole, Susannah and Olson, Michael R. and Hay, Bruce A. (2002) Drosophila Bruce Can Potently Suppress Rpr- and Grim-Dependent but Not Hid-Dependent Cell Death. Current Biology, 12 (13). pp. 1164-1168. ISSN 0960-9822. doi:10.1016/s0960-9822(02)00935-1.

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Bruce is a large protein (530 kDa) that contains an N-terminal baculovirus IAP repeat (BIR) and a C-terminal ubiquitin conjugation domain (E2) 1, 2. BRUCE upregulation occurs in some cancers and contributes to the resistance of these cells to DNA-damaging chemotherapeutic drugs [2]. However, it is still unknown whether Bruce inhibits apoptosis directly or instead plays some other more indirect role in mediating chemoresistance, perhaps by promoting drug export, decreasing the efficacy of DNA damage-dependent cell death signaling, or by promoting DNA repair. Here, we demonstrate, using gain-of-function and deletion alleles, that Drosophila Bruce (dBruce) can potently inhibit cell death induced by the essential Drosophila cell death activators Reaper (Rpr) and Grim but not Head involution defective (Hid). The dBruce BIR domain is not sufficient for this activity, and the E2 domain is likely required. dBruce does not promote Rpr or Grim degradation directly, but its antiapoptotic actions do require that their N termini, required for interaction with DIAP1 BIR2, be intact. dBruce does not block the activity of the apical cell death caspase Dronc or the proapoptotic Bcl-2 family member Debcl/Drob-1/dBorg-1/Dbok. Together, these results argue that dBruce can regulate cell death at a novel point.

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Additional Information:© 2002 Cell Press. Published by Elsevier Ltd. Received 25 April 2002, Revised 9 May 2002, Accepted 29 May 2002, Available online 17 July 2002. We thank John Nambu and Sharad Kumar for providing fly stocks, Pat Koen for assistance with SEM, Lijuan Wang for assistance with protein purification, Hong Yu for assistance with Rpr and Grim construct generation, and Sally Kornbluth for the Rpr-lys− transgene. This work was supported by grants to B.A.H. from Amgen and National Institutes of Health grant GM057422. Accession Numbers: The GenBank accession number for the dBruce exon-intron structure reported in this paper is AF517634.
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Issue or Number:13
Record Number:CaltechAUTHORS:20200427-151127652
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Official Citation:Stephanie Y. Vernooy, Vivian Chow, Julius Su, Koen Verbrugghe, Jennifer Yang, Susannah Cole, Michael R. Olson, Bruce A. Hay, Drosophila Bruce Can Potently Suppress Rpr- and Grim-Dependent but Not Hid-Dependent Cell Death, Current Biology, Volume 12, Issue 13, 2002, Pages 1164-1168, ISSN 0960-9822, (
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:102818
Deposited By: Tony Diaz
Deposited On:27 Apr 2020 22:30
Last Modified:16 Nov 2021 18:15

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