Oncotarget

Research Papers:

Proapoptotic function of deubiquitinase DUSP31 in Drosophila

Sergey A. Sinenko _

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Oncotarget. 2017; 8:70452-70462. https://doi.org/10.18632/oncotarget.19715

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Abstract

Sergey A. Sinenko1,2

1Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA

2Institute of Cytology, Russian Academy of Sciences, Saint Petersburg 194064, Russia

Correspondence to:

Sergey A. Sinenko, email: [email protected]

Keywords: apoptosis, deubitiquinase, DUSP31, Dark, Drosophila

Received: May 27, 2017     Accepted: June 26, 2017     Published: July 31, 2017

ABSTRACT

Drosophila have been used to identify new components in apoptosis regulation. The Drosophila protein Dark forms an octameric apoptosome complex that induces the initiator caspase Dronc to trigger the caspase cell death pathway and, therefore, plays an important role in controlling apoptosis. Caspases and Dark are constantly expressed in cells, but their activity is blocked by DIAP1 E3 ligase-mediated ubiquitination and subsequent inactivation or proteasomal degradation. One of the regulatory mechanisms that stabilize proapoptotic factors is the removal of ubiquitin chains by deubiquitinases. In this study performed a modified genetic screen for deubiquitinases (dsRNA lines) to identify those involved in stabilizing proapoptotic components. Loss-of-function alleles of deubiquitinase DUSP31 were identified as suppressors of the Dronc overexpression phenotype. DUSP31 deficiency also suppresses apoptosis induced by the RHG protein, Grim. Genetic analysis revealed for the first time that DUSP31 deficiency sufficiently suppresses the Dark phenotype, indicating its involvement in the control of Dark/Dronc apoptosome function in invertebrate apoptosis.


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