Li Mingli, Lindblad Jillian L, Perez Ernesto, Bergmann Andreas, Fan Yun
University of Birmingham, School of Biosciences, Edgbaston, Birmingham, B15 2TT, UK.
Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, 364 Plantation Street, LRB419, Worcester, MA, 01605, USA.
BMC Biol. 2016 Aug 19;14:70. doi: 10.1186/s12915-016-0293-y.
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.
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.
In addition to a role of dAtg1 in autophagy and neuronal development, we report a third function of dAtg1 for AiP.
ATG1属于Uncoordinated-51样激酶蛋白家族。该家族成员在巨自噬和神经元发育中的作用最为显著。凋亡诱导增殖（AiP）是一种由半胱天冬酶介导且依赖JNK的过程，参与大规模应激诱导的凋亡细胞丢失后的组织修复和再生。在某些情况下，AiP可导致组织过度生长，与癌症相关。
在此，我们表明果蝇中的Atg1（dAtg1）在眼和翅成虫盘的再生及促进过度生长的AiP过程中具有先前未被认识的功能。dAtg1在遗传上位于JNK活性的下游，并受其转录诱导，且它是JNK依赖性产生如Wingless等有丝分裂原以促进AiP所必需的。有趣的是，dAtg1在AiP中的这一功能与其在自噬和神经元发育中的作用无关。
除了dAtg1在自噬和神经元发育中的作用外，我们报道了dAtg1在AiP中的第三种功能。
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