High levels of dRYBP induce apoptosis in Drosophila imaginal cells through the activation of reaper and the requirement of trithorax, dredd and dFADD.
Drosophila RYBP (dRYBP; Ring1 and YY1 Binding Protein) is a Polycomb and trithorax interacting protein, whose homologous RYBP/DEDAF mammalian counterparts exhibit tumor cell-specific killing activity. Here we show that although endogenous dRYBP is not involved in developmental apoptosis, high levels of exogenous dRYBP induce apoptosis in all the imaginal discs of the fly, indicating that dRYBP apoptotic activity is not specific to tumor cells. We also show that dRYBP-induced apoptosis is inhibited by high levels of either p35 or DIAP1 (Drosophila Inhibitor of Apoptosis Protein 1), and requires the function of the pro-apoptotic REAPER, HID and GRIM proteins, the apical caspase DREDD, the adaptor dFADD protein as well as TRITHORAX (TRX), an epigenetic transcriptional regulator. Furthermore, we demonstrate that overexpression of TRX also induces apoptosis in the imaginal discs. Finally, we show that the expression of reaper-lacZ is upregulated both upon dRYBP-induced apoptosis and upon TRX-induced apoptosis in imaginal discs and that the reaper gene is a direct target of dRYBP in Drosophila embryos. Our results indicate that dRYBP triggers in a receptor-mediated apoptotic pathway that also includes TRX-dependent epigenetic regulation of gene expression.
González
Inma
I
Centro de Biología Molecular Severo Ochoa CSIC-UAM, c) Nicolás Cabrera 1, Universidad Autónoma de Madrid, Campus de Cantoblanco, Madrid, Spain.
Busturia
Ana
A
D000818:Animals; D017209:Apoptosis; D020169:Caspases / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D004330:Drosophila / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D053200:Fas-Associated Death Domain Protein / Q000378:metabolism*; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins / Q000378:metabolism*
D002868:Chromosomal Proteins, Non-Histone; C111891:DIAP1 protein, Drosophila; D029721:Drosophila Proteins; C469219:FADD protein, Drosophila; D053200:Fas-Associated Death Domain Protein; D051034:Inhibitor of Apoptosis Proteins; C507389:RYBP protein, Drosophila; D012097:Repressor Proteins; C086973:rpr protein, Drosophila; C512571:trx protein, Drosophila; D048031:JNK Mitogen-Activated Protein Kinases; D020169:Caspases; C431887:dredd protein, Drosophila