title: Beclin 1-independent autophagy induced by a Bcl-XL/Bcl-2 targeting compound, Z18.
abstract: Inhibitors of Bcl-XL/Bcl-2 can induce autophagy by releasing the autophagic protein Beclin 1 from its complexes with these proteins. Here we report a novel compound targeting the BH3 binding groove of Bcl-XL/Bcl-2, Z18, which efficiently induces autophagy-associated cell death in HeLa cells, without apparent apoptosis. Unexpectedly, the inhibition of Beclin 1 and phosphatidylinositol 3-kinase have no obvious effect on Z18-induced autophagy in HeLa cells, implying that it is a non-canonical Beclin 1-independent autophagy. Meanwhile, the accumulation of autophagosomes is positively correlated with Z18-induced cell death and the full flux of autophagy is not necessary.
authors.affiliation: Beijing Nuclear Magnetic Resonance Center, College of Chemistry and Molecular Engineering, and College of Life Sciences, Peking University; Beijing, China.
authors.forename: Songhai
authors.initials: S
authors.lastname: Tian
authors.forename: Jian
authors.initials: J
authors.lastname: Lin
authors.forename: Jian
authors.initials: J
authors.lastname: Jun Zhou
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Wang
authors.forename: Yanjun
authors.initials: Y
authors.lastname: Li
authors.forename: Xiaobai
authors.initials: X
authors.lastname: Ren
authors.forename: Wenyu
authors.initials: W
authors.lastname: Yu
authors.forename: Wu
authors.initials: W
authors.lastname: Zhong
authors.forename: Junhai
authors.initials: J
authors.lastname: Xiao
authors.forename: Fugeng
authors.initials: F
authors.lastname: Sheng
authors.forename: Yingyu
authors.initials: Y
authors.lastname: Chen
authors.forename: Changwen
authors.initials: C
authors.lastname: Jin
authors.forename: Song
authors.initials: S
authors.lastname: Li
authors.forename: Zhibing
authors.initials: Z
authors.lastname: Zheng
authors.forename: Bin
authors.initials: B
authors.lastname: Xia
mesh_terms: D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001343:Autophagy / Q000187:drug effects*; D000071186:Beclin-1; D001665:Binding Sites; D006367:HeLa Cells; D006801:Humans; D007211:Indoles / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D008565:Membrane Proteins / Q000378:metabolism; D008954:Models, Biological; D013876:Thiophenes / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D051020:bcl-X Protein / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; D007211:Indoles; D008565:Membrane Proteins; D013876:Thiophenes; D051020:bcl-X Protein