Fig. 3

CaMKII induces autophagy through phosphorylation of Beclin 1 at Ser90 and the subsequent ubiquitination at Lys117. a Dissociation of the Bcl-2-Beclin 1 Complex. SK-N-SH cells treated with 6 μM ionomycin or 100 nM EB1089 were lysed and incubated with anti-Beclin 1 or normal mouse IgG antibodies prior to western blot analysis. The resulting immunoprecipitates were subjected to western blot analysis using the indicated antibodies. TCL, whole-cell lysate. b Autophagy induced by ionomycin in neuroblastoma cells. Both cell lines were treated with 6 μM ionomycin for the indicated periods or various concentrations of ionomycin for 24 h. The total cell lysates were analyzed for LC3 lipidation by immunoblotting. c LC3 mRNA expression was unaffected in cells treated with ionomycin or EB1089. The SK-N-SH cells were untreated or were treated with ionomycin or EB1089 of indicated concentration for 24 h. The expression level of LC3 mRNA was detected by real-time RT-PCR. The error bars represent the standard deviations (SD) calculated from three parallel experiments. d LC3 lipidation and p62 degradation in CaMKII-KD-expressing MEFs cells or control cells (Ctrl). MEFs cells transfected with a control vector or plasmids encoding His-CaMKII-KD were treated with 6 μM ionomycin for 24 h, then incubated for 2 h in the presence or absence of 100 nM Baf A1. The whole-cell extracts were subjected to western blot using the indicated antibodies. e LC3 lipidation and p62 degradation in CaMKII shRNA MEFs cells or negative control cells (NC). MEFs cells transfected with negative control or CaMKII shRNA were treated with 6 μM ionomycin for 24 h, then incubated for 2 h in the presence or absence of 100 nM Baf A1. The whole-cell extracts were subjected to western blot using the indicated antibodies. f LC3 lipidation in Beclin 1-deficient MEFs expressing WT Beclin 1 or S90A-Beclin 1. The cells were incubated in 6 μM ionomycin for 24 h, and total cell lysates were analyzed for LC3 lipidation by means of immunoblotting. g Autophagosome formation in MEFs deficient for Beclin 1. The cells were incubated in 6 μM ionomycin for 24 h and then fixed. LC3-positive puncta were shown as the means ± SEM of five random areas. **P < 0.01, Student’s t-test. Scale bar, 10 μm