Autophagy-independent function of Atg1 for apoptosis-induced compensatory proliferation

BMC Biol. 2016 Aug 19:14:70. doi: 10.1186/s12915-016-0293-y.

Abstract

Background: ATG1 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.

Results: Here, 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.

Conclusion: In addition to a role of dAtg1 in autophagy and neuronal development, we report a third function of dAtg1 for AiP.

Keywords: Apoptosis-induced proliferation; Atg1; Autophagy; Jun-N-terminal kinase signaling; ULK1/2.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Apoptosis*
  • Autophagy*
  • Autophagy-Related Protein-1 Homolog / genetics
  • Autophagy-Related Protein-1 Homolog / metabolism*
  • Cell Proliferation
  • Drosophila / genetics*
  • Drosophila / metabolism
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Eye / growth & development
  • Imaginal Discs / growth & development
  • MAP Kinase Signaling System
  • Transcriptional Activation
  • Wings, Animal / growth & development

Substances

  • Drosophila Proteins
  • Atg1 protein, Drosophila
  • Autophagy-Related Protein-1 Homolog