The antileukemic activities of GADD45g are mediated through inhibition of E2F1 via the p38 MAPK–dependent signaling pathway. (A) Significantly enriched GSEA signatures in the transcriptional profile of Molm-13 cells upon GADD45g overexpression. The normalized enrichment score (NES) and P values are shown. (B) Correlation of expression between GADD45g and E2F1 in BMMNCs from AML samples (n = 56). Correlation coefficient and P value of Spearman correlation test are shown. (C) Molm-13 cells and (left) and THP-1 cells (right) with or without Dox-induced GADD45g overexpression were treated with 1 μM SB203580 for 16 hours and then subjected to western blot to detect the indicated proteins. (D) Molm-13 cells and THP-1 cells with or without Dox-induced GADD45g overexpression were treated with 1 μM SB203580 for 16 hours. Relative mRNA expression of E2F1 was quantified by qRT-PCR. Molm-13 cells with or without Dox-induced GADD45g overexpression were treated with 1 μM SB203580 (E) or transduced with lentiviral vectors expressing E2F1 (F), and the percentage of apoptosis cells was determined by fluorescence-activated cell sorting (FACS) analysis of Annexin V and 7AAD staining. Molm-13 cells with or without Dox-induced GADD45g overexpression were treated with 1 μM SB203580 (G) or transduced with lentiviral vectors expressing E2F1 (H). Representative IF micrographs (left) showing γH2AX foci from 3 independent experiments and quantification (right) of γH2AX foci (red) in nuclei (blue) per cell. Scale bar, 5 μm. Data are presented as the mean ± SD of ≥3 independent experiments, and comparisons were evaluated by using the 2-tailed Student t test. Correlations between continuous variables were calculated by using the Pearson correlation. *P < .05, **P < .01, ***P < .001, ****P < .0001. DMSO, dimethyl sulfoxide; NS, not significant.
Figure 5.

The antileukemic activities of GADD45g are mediated through inhibition of E2F1 via the p38 MAPK–dependent signaling pathway. (A) Significantly enriched GSEA signatures in the transcriptional profile of Molm-13 cells upon GADD45g overexpression. The normalized enrichment score (NES) and P values are shown. (B) Correlation of expression between GADD45g and E2F1 in BMMNCs from AML samples (n = 56). Correlation coefficient and P value of Spearman correlation test are shown. (C) Molm-13 cells and (left) and THP-1 cells (right) with or without Dox-induced GADD45g overexpression were treated with 1 μM SB203580 for 16 hours and then subjected to western blot to detect the indicated proteins. (D) Molm-13 cells and THP-1 cells with or without Dox-induced GADD45g overexpression were treated with 1 μM SB203580 for 16 hours. Relative mRNA expression of E2F1 was quantified by qRT-PCR. Molm-13 cells with or without Dox-induced GADD45g overexpression were treated with 1 μM SB203580 (E) or transduced with lentiviral vectors expressing E2F1 (F), and the percentage of apoptosis cells was determined by fluorescence-activated cell sorting (FACS) analysis of Annexin V and 7AAD staining. Molm-13 cells with or without Dox-induced GADD45g overexpression were treated with 1 μM SB203580 (G) or transduced with lentiviral vectors expressing E2F1 (H). Representative IF micrographs (left) showing γH2AX foci from 3 independent experiments and quantification (right) of γH2AX foci (red) in nuclei (blue) per cell. Scale bar, 5 μm. Data are presented as the mean ± SD of ≥3 independent experiments, and comparisons were evaluated by using the 2-tailed Student t test. Correlations between continuous variables were calculated by using the Pearson correlation. *P < .05, **P < .01, ***P < .001, ****P < .0001. DMSO, dimethyl sulfoxide; NS, not significant.

This Feature Is Available To Subscribers Only

or Create an Account

Close Modal
Close Modal