A novel dRYBP-SCF complex functions to inhibit apoptosis in Drosophila.
Apoptosis
; 18(12): 1500-12, 2013 Dec.
Article
em En
| MEDLINE
| ID: mdl-23979704
ABSTRACT
A balanced response to intrinsic and extrinsic apoptotic signals is crucial to support homeostatic development and animal survival. Regulation of activation and inhibition of apoptotic pathways involves diverse mechanisms including protein ubiquitylation to control expression levels of apoptotic factors. Here we report that drosophila Ring and YY1 Binding Protein (dRYBP) protein interacts both genetically and biochemically with the E3 ubiquitin ligase SKPA, dCULLIN, F-box (SCF) complex to synergistically inhibit apoptosis in Drosophila. Further, we show that the loss of skpA function activates the intrinsic pathway of apoptosis and down-regulates the levels of expression of the anti-apoptotic DIAP1 protein. Accordingly, the apoptosis induced by inactivation of skpA and dRYBP is rescued by loss of function of the pro-apoptotic gene reaper and overexpression of DIAP1. Of interest, we also find that high levels of SKPA protein rescue the wing phenotype induced by overexpression of Reaper protein. Finally, we demonstrate that overexpression of SKPA inhibits both developmental and radiation-induced apoptosis. We propose that the function of the dRYBP-SCF complex in the inhibition of apoptosis might possibly be to control the levels of the pro-apoptotic and anti-apoptotic proteins most likely by promoting their ubiquitylation and consequently, proteasomal degradation. Given the evolutionary conservation of the dRYBP and the SCF proteins, our results suggest that their mammalian homologs may function in balancing cell survival versus cell death during normal and pathological development.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Proteínas Repressoras
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Proteínas de Ligação ao Cálcio
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Proteínas Nucleares
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Regulação para Baixo
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Apoptose
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Proteínas de Drosophila
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Drosophila melanogaster
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article