Beclin 1-independent autophagy induced by a Bcl-XL/Bcl-2 targeting compound, Z18.
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.
Tian
Songhai
S
Beijing Nuclear Magnetic Resonance Center, College of Chemistry and Molecular Engineering, and College of Life Sciences, Peking University; Beijing, China.
Lin
Jian
J
Jun Zhou
Jian
J
Wang
Xiaolong
X
Li
Yanjun
Y
Ren
Xiaobai
X
Yu
Wenyu
W
Zhong
Wu
W
Xiao
Junhai
J
Sheng
Fugeng
F
Chen
Yingyu
Y
Jin
Changwen
C
Li
Song
S
Zheng
Zhibing
Z
Xia
Bin
B
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
D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; D007211:Indoles; D008565:Membrane Proteins; D013876:Thiophenes; D051020:bcl-X Protein