The initiator caspase Dronc is subject of enhanced autophagy upon proteasome impairment in Drosophila.
A major function of ubiquitylation is to deliver target proteins to the proteasome for degradation. In the apoptotic pathway in Drosophila, the inhibitor of apoptosis protein 1 (Diap1) regulates the activity of the initiator caspase Dronc (death regulator Nedd2-like caspase; caspase-9 ortholog) by ubiquitylation, supposedly targeting Dronc for degradation by the proteasome. Using a genetic approach, we show that Dronc protein fails to accumulate in epithelial cells with impaired proteasome function suggesting that it is not degraded by the proteasome, contrary to the expectation. Similarly, decreased autophagy, an alternative catabolic pathway, does not result in increased Dronc protein levels. However, combined impairment of the proteasome and autophagy triggers accumulation of Dronc protein levels suggesting that autophagy compensates for the loss of the proteasome with respect to Dronc turnover. Consistently, we show that loss of the proteasome enhances endogenous autophagy in epithelial cells. We propose that enhanced autophagy degrades Dronc if proteasome function is impaired.
Department of Biochemistry and Molecular Biology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
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Lee
Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA, USA.
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Kamber Kaya
Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA, USA.
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Simin
Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA, USA.
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Baehrecke
Department of Biochemistry and Molecular Biology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.|Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA, USA.
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0000-0002-9134-871X
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Bergmann
D000818:Animals; D017209:Apoptosis; D001343:Autophagy; D020169:Caspases / Q000378:metabolism*; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D010450:Endopeptidases / Q000378:metabolism; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism; D016296:Mutagenesis; D046988:Proteasome Endopeptidase Complex / Q000235:genetics / Q000378:metabolism*; D021122:Protein Subunits / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D054875:Ubiquitination
C111891:DIAP1 protein, Drosophila; D029721:Drosophila Proteins; D051034:Inhibitor of Apoptosis Proteins; D021122:Protein Subunits; D034741:RNA, Small Interfering; D010450:Endopeptidases; C514943:Prosbeta2 protein, Drosophila; D020169:Caspases; C118731:dronc protein, Drosophila; D046988:Proteasome Endopeptidase Complex