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The deubiquitinating enzyme DUBAI stabilizes DIAP1 to suppress Drosophila apoptosis.

Publication ,  Journal Article
Yang, C-S; Sinenko, SA; Thomenius, MJ; Robeson, AC; Freel, CD; Horn, SR; Kornbluth, S
Published in: Cell Death Differ
April 2014

Deubiquitinating enzymes (DUBs) counteract ubiquitin ligases to modulate the ubiquitination and stability of target signaling molecules. In Drosophila, the ubiquitin-proteasome system has a key role in the regulation of apoptosis, most notably, by controlling the abundance of the central apoptotic regulator DIAP1. Although the mechanism underlying DIAP1 ubiquitination has been extensively studied, the precise role of DUB(s) in controlling DIAP1 activity has not been fully investigated. Here we report the identification of a DIAP1-directed DUB using two complementary approaches. First, a panel of putative Drosophila DUBs was expressed in S2 cells to determine whether DIAP1 could be stabilized, despite treatment with death-inducing stimuli that would induce DIAP1 degradation. In addition, RNAi fly lines were used to detect modifiers of DIAP1 antagonist-induced cell death in the developing eye. Together, these approaches identified a previously uncharacterized protein encoded by CG8830, which we named DeUBiquitinating-Apoptotic-Inhibitor (DUBAI), as a novel DUB capable of preserving DIAP1 to dampen Drosophila apoptosis. DUBAI interacts with DIAP1 in S2 cells, and the putative active site of its DUB domain (C367) is required to rescue DIAP1 levels following apoptotic stimuli. DUBAI, therefore, represents a novel locus of apoptotic regulation in Drosophila, antagonizing cell death signals that would otherwise result in DIAP1 degradation.

Duke Scholars

Published In

Cell Death Differ

DOI

EISSN

1476-5403

Publication Date

April 2014

Volume

21

Issue

4

Start / End Page

604 / 611

Location

England

Related Subject Headings

  • Ubiquitination
  • Temperature
  • RNA Interference
  • Protein Structure, Tertiary
  • Protein Binding
  • Inhibitor of Apoptosis Proteins
  • Eye
  • Endopeptidases
  • Drosophila Proteins
  • Drosophila
 

Citation

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Yang, C.-S., Sinenko, S. A., Thomenius, M. J., Robeson, A. C., Freel, C. D., Horn, S. R., & Kornbluth, S. (2014). The deubiquitinating enzyme DUBAI stabilizes DIAP1 to suppress Drosophila apoptosis. Cell Death Differ, 21(4), 604–611. https://doi.org/10.1038/cdd.2013.184
Yang, C. -. S., S. A. Sinenko, M. J. Thomenius, A. C. Robeson, C. D. Freel, S. R. Horn, and S. Kornbluth. “The deubiquitinating enzyme DUBAI stabilizes DIAP1 to suppress Drosophila apoptosis.Cell Death Differ 21, no. 4 (April 2014): 604–11. https://doi.org/10.1038/cdd.2013.184.
Yang C-S, Sinenko SA, Thomenius MJ, Robeson AC, Freel CD, Horn SR, et al. The deubiquitinating enzyme DUBAI stabilizes DIAP1 to suppress Drosophila apoptosis. Cell Death Differ. 2014 Apr;21(4):604–11.
Yang, C. .. S., et al. “The deubiquitinating enzyme DUBAI stabilizes DIAP1 to suppress Drosophila apoptosis.Cell Death Differ, vol. 21, no. 4, Apr. 2014, pp. 604–11. Pubmed, doi:10.1038/cdd.2013.184.
Yang C-S, Sinenko SA, Thomenius MJ, Robeson AC, Freel CD, Horn SR, Kornbluth S. The deubiquitinating enzyme DUBAI stabilizes DIAP1 to suppress Drosophila apoptosis. Cell Death Differ. 2014 Apr;21(4):604–611.

Published In

Cell Death Differ

DOI

EISSN

1476-5403

Publication Date

April 2014

Volume

21

Issue

4

Start / End Page

604 / 611

Location

England

Related Subject Headings

  • Ubiquitination
  • Temperature
  • RNA Interference
  • Protein Structure, Tertiary
  • Protein Binding
  • Inhibitor of Apoptosis Proteins
  • Eye
  • Endopeptidases
  • Drosophila Proteins
  • Drosophila