Abstract
BackgroundATG1 belongs to the Uncoordinated-51-like kinase protein family. Members of this family are best characterized for roles in macroautophagy and neuronal development. Apoptosis-induced proliferation (AiP) is a caspase-directed and JNK-dependent process which is involved in tissue repair and regeneration after massive stress-induced apoptotic cell loss. Under certain conditions, AiP can cause tissue overgrowth with implications for cancer.ResultsHere, we show that Atg1 in Drosophila (dAtg1) has a previously unrecognized function for both regenerative and overgrowth-promoting AiP in eye and wing imaginal discs. dAtg1 acts genetically downstream of and is transcriptionally induced by JNK activity, and it is required for JNK-dependent production of mitogens such as Wingless for AiP. Interestingly, this function of dAtg1 in AiP is independent of its roles in autophagy and in neuronal development.ConclusionIn addition to a role of dAtg1 in autophagy and neuronal development, we report a third function of dAtg1 for AiP.Electronic supplementary materialThe online version of this article (doi:10.1186/s12915-016-0293-y) contains supplementary material, which is available to authorized users.
Highlights
ATG1 belongs to the Uncoordinated-51-like kinase protein family
Autophagy-related gene 1 (Atg1) in yeast, dAtg1 in Drosophila, uncoordinated-51 in C. elegans, and Unc-51-like kinase 1 and 2 (ULK1/2) in mammals are members of the evolutionary conserved Uncoordinated51-like kinase (ULK) protein kinase family that play critical roles in macroautophagy and neuronal development
Results dAtg1 is a suppressor of apoptosis-induced proliferation Apoptosis-induced proliferation (AiP) phenotypes of ey > hid-p35 animals vary from mild to moderate to severe overgrowth of head capsules characterized by pattern duplications of ocelli, bristles, and sometimes entire antennae as well as deformed heads with amorphic tissue (Fig. 1a–d) [52]
Summary
ATG1 belongs to the Uncoordinated-51-like kinase protein family. Members of this family are best characterized for roles in macroautophagy and neuronal development. Autophagy-related gene 1 (Atg1) in yeast, dAtg in Drosophila, uncoordinated-51 (unc-51) in C. elegans, and Unc-51-like kinase 1 and 2 (ULK1/2) in mammals are members of the evolutionary conserved Uncoordinated51-like kinase (ULK) protein kinase family that play critical roles in macroautophagy (referred to as autophagy) and neuronal development (reviewed in [1, 2]). Genetic studies in yeast identified Atg as an essential gene required for the initiation of autophagy [3,4,5]. This function of ULK proteins is conserved in evolution [6,7,8,9]. Critical components in these ubiquitin-like conjugation systems are ATG7 (E1), ATG10 and ATG3 (E2s), as well as another protein complex, ATG5-ATG12ATG16, which serves as an E3 ligase for ATG8/LC3
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