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A The frequency of p53 mutation in Diffuse Large B Cell lymphoma (DLBC) patients (DFCI, Nat Med, 2018 ), (Broad, PNAS, 2012), (BCGSC, Blood, 2013 ), (TCGA, PanCancer Atlas), (Duke, Cell, 2017) , ALL patients (St Jude, Nat Genet, 2016), (St Jude, Nat Genet, 2015) , and pediatric ALL patients (TARGET, 2018)—across public datasets in https://www.cbioportal.org . B U2OS cells were transfected with an empty or FLT4 expression plasmid along with a pg13 luciferase reporter vector or a luciferase reporter for p21 or MDM2 to determine p53 target genes activity. C U2OS cells were transfected with an empty or FLT4 expression vector for 24 h. The cells were then treated with 10 µg/mL of 5-FU for 6 h. The cell lysates were blotted for the indicated antibodies. D U2OS cells were transfected with different combinations of FLT4, MDM2, and MDMX plasmids along with pg13 luciferase reporter vector to determine endogenous p53 under genotoxic conditions with 5-FU. E HEK293T cells were transfected with various amounts of FLT4 expression plasmid for 24 h. The cell lysates were blotted for the indicated antibodies. F HEK293T cells were transfected with a combination of FLT4, MDMX and MDM2 expression plasmids for 24 h. The cell lysates were blotted for the indicated antibodies (LE low exposure, HE high exposure). G U2OS cells were transfected with a combination of FLT4, MDMX or MDM2 expression plasmids for 24 h. The cell lysates were blotted for the indicated antibodies. H U2OS cells were transfected with a combination of FLT4, MDMX, wild-type MDM2 or mutant MDM2 <t>C464A</t> expression plasmids for 24 h. The cell lysates were blotted for the indicated antibodies. I U2OS cells were transfected with a combination of FLT4, MDMX, and MDM2 expression plasmids and immunostained for MDMX (green) and MDM2 (red), while the nuclei were stained with Hoechst. Scale bar: 20 μm. * p < 0.05, **** p < 0.0001.
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Image Search Results


A The frequency of p53 mutation in Diffuse Large B Cell lymphoma (DLBC) patients (DFCI, Nat Med, 2018 ), (Broad, PNAS, 2012), (BCGSC, Blood, 2013 ), (TCGA, PanCancer Atlas), (Duke, Cell, 2017) , ALL patients (St Jude, Nat Genet, 2016), (St Jude, Nat Genet, 2015) , and pediatric ALL patients (TARGET, 2018)—across public datasets in https://www.cbioportal.org . B U2OS cells were transfected with an empty or FLT4 expression plasmid along with a pg13 luciferase reporter vector or a luciferase reporter for p21 or MDM2 to determine p53 target genes activity. C U2OS cells were transfected with an empty or FLT4 expression vector for 24 h. The cells were then treated with 10 µg/mL of 5-FU for 6 h. The cell lysates were blotted for the indicated antibodies. D U2OS cells were transfected with different combinations of FLT4, MDM2, and MDMX plasmids along with pg13 luciferase reporter vector to determine endogenous p53 under genotoxic conditions with 5-FU. E HEK293T cells were transfected with various amounts of FLT4 expression plasmid for 24 h. The cell lysates were blotted for the indicated antibodies. F HEK293T cells were transfected with a combination of FLT4, MDMX and MDM2 expression plasmids for 24 h. The cell lysates were blotted for the indicated antibodies (LE low exposure, HE high exposure). G U2OS cells were transfected with a combination of FLT4, MDMX or MDM2 expression plasmids for 24 h. The cell lysates were blotted for the indicated antibodies. H U2OS cells were transfected with a combination of FLT4, MDMX, wild-type MDM2 or mutant MDM2 C464A expression plasmids for 24 h. The cell lysates were blotted for the indicated antibodies. I U2OS cells were transfected with a combination of FLT4, MDMX, and MDM2 expression plasmids and immunostained for MDMX (green) and MDM2 (red), while the nuclei were stained with Hoechst. Scale bar: 20 μm. * p < 0.05, **** p < 0.0001.

Journal: Oncogenesis

Article Title: FLT4 activation promotes acute lymphoid leukemia survival through stabilization of MDM2/MDMX and inactivation of p53

doi: 10.1038/s41389-025-00552-7

Figure Lengend Snippet: A The frequency of p53 mutation in Diffuse Large B Cell lymphoma (DLBC) patients (DFCI, Nat Med, 2018 ), (Broad, PNAS, 2012), (BCGSC, Blood, 2013 ), (TCGA, PanCancer Atlas), (Duke, Cell, 2017) , ALL patients (St Jude, Nat Genet, 2016), (St Jude, Nat Genet, 2015) , and pediatric ALL patients (TARGET, 2018)—across public datasets in https://www.cbioportal.org . B U2OS cells were transfected with an empty or FLT4 expression plasmid along with a pg13 luciferase reporter vector or a luciferase reporter for p21 or MDM2 to determine p53 target genes activity. C U2OS cells were transfected with an empty or FLT4 expression vector for 24 h. The cells were then treated with 10 µg/mL of 5-FU for 6 h. The cell lysates were blotted for the indicated antibodies. D U2OS cells were transfected with different combinations of FLT4, MDM2, and MDMX plasmids along with pg13 luciferase reporter vector to determine endogenous p53 under genotoxic conditions with 5-FU. E HEK293T cells were transfected with various amounts of FLT4 expression plasmid for 24 h. The cell lysates were blotted for the indicated antibodies. F HEK293T cells were transfected with a combination of FLT4, MDMX and MDM2 expression plasmids for 24 h. The cell lysates were blotted for the indicated antibodies (LE low exposure, HE high exposure). G U2OS cells were transfected with a combination of FLT4, MDMX or MDM2 expression plasmids for 24 h. The cell lysates were blotted for the indicated antibodies. H U2OS cells were transfected with a combination of FLT4, MDMX, wild-type MDM2 or mutant MDM2 C464A expression plasmids for 24 h. The cell lysates were blotted for the indicated antibodies. I U2OS cells were transfected with a combination of FLT4, MDMX, and MDM2 expression plasmids and immunostained for MDMX (green) and MDM2 (red), while the nuclei were stained with Hoechst. Scale bar: 20 μm. * p < 0.05, **** p < 0.0001.

Article Snippet: Expression plasmids, including pCMV-Myc-MDM2, pCMV-MDM2 C464A mutant, pcDNA3-FLT4, and pcDNA3-Flag-MDMX, were obtained from Addgene (#16441, #12086, #119230, and previously described [ ], respectively).

Techniques: Mutagenesis, Transfection, Expressing, Plasmid Preparation, Luciferase, Activity Assay, Staining