MDM2 Inhibitor, Nutlin 3a, Induces p53 Dependent Autophagy in Acute Leukemia by AMP Kinase Activation.
MDM2 (mouse double minute 2) inhibitors that activate p53 and induce apoptosis in a non-genotoxic manner are in clinical development for treatment of leukemias. P53 can modulate other programmed cell death pathways including autophagy both transcriptionally and non-transcriptionally. We investigated...
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doaj-1e29b2e8f776433bb52a37ec5080a36e2020-11-25T02:36:43ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-011010e013925410.1371/journal.pone.0139254MDM2 Inhibitor, Nutlin 3a, Induces p53 Dependent Autophagy in Acute Leukemia by AMP Kinase Activation.Gautam BorthakurSeshagiri DuvvuriVivian RuvoloDurga Nand TripathiSujan PiyaJared BurksRodrigo JacamoKensuke KojimaPeter RuvoloJuan Fueyo-MargaretoMarina KonoplevaMichael AndreeffMDM2 (mouse double minute 2) inhibitors that activate p53 and induce apoptosis in a non-genotoxic manner are in clinical development for treatment of leukemias. P53 can modulate other programmed cell death pathways including autophagy both transcriptionally and non-transcriptionally. We investigated autophagy induction in acute leukemia by Nutlin 3a, a first-in-class MDM2 inhibitor. Nutlin 3a induced autophagy in a p53 dependent manner and transcriptional activation of AMP kinase (AMPK) is critical, as this effect is abrogated in AMPK -/- mouse embryonic fibroblasts. Nutlin 3a induced autophagy appears to be pro-apoptotic as pharmacological (bafilomycin) or genetic inhibition (BECLIN1 knockdown) of autophagy impairs apoptosis induced by Nutlin 3a.http://europepmc.org/articles/PMC4595506?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Gautam Borthakur Seshagiri Duvvuri Vivian Ruvolo Durga Nand Tripathi Sujan Piya Jared Burks Rodrigo Jacamo Kensuke Kojima Peter Ruvolo Juan Fueyo-Margareto Marina Konopleva Michael Andreeff |
spellingShingle |
Gautam Borthakur Seshagiri Duvvuri Vivian Ruvolo Durga Nand Tripathi Sujan Piya Jared Burks Rodrigo Jacamo Kensuke Kojima Peter Ruvolo Juan Fueyo-Margareto Marina Konopleva Michael Andreeff MDM2 Inhibitor, Nutlin 3a, Induces p53 Dependent Autophagy in Acute Leukemia by AMP Kinase Activation. PLoS ONE |
author_facet |
Gautam Borthakur Seshagiri Duvvuri Vivian Ruvolo Durga Nand Tripathi Sujan Piya Jared Burks Rodrigo Jacamo Kensuke Kojima Peter Ruvolo Juan Fueyo-Margareto Marina Konopleva Michael Andreeff |
author_sort |
Gautam Borthakur |
title |
MDM2 Inhibitor, Nutlin 3a, Induces p53 Dependent Autophagy in Acute Leukemia by AMP Kinase Activation. |
title_short |
MDM2 Inhibitor, Nutlin 3a, Induces p53 Dependent Autophagy in Acute Leukemia by AMP Kinase Activation. |
title_full |
MDM2 Inhibitor, Nutlin 3a, Induces p53 Dependent Autophagy in Acute Leukemia by AMP Kinase Activation. |
title_fullStr |
MDM2 Inhibitor, Nutlin 3a, Induces p53 Dependent Autophagy in Acute Leukemia by AMP Kinase Activation. |
title_full_unstemmed |
MDM2 Inhibitor, Nutlin 3a, Induces p53 Dependent Autophagy in Acute Leukemia by AMP Kinase Activation. |
title_sort |
mdm2 inhibitor, nutlin 3a, induces p53 dependent autophagy in acute leukemia by amp kinase activation. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2015-01-01 |
description |
MDM2 (mouse double minute 2) inhibitors that activate p53 and induce apoptosis in a non-genotoxic manner are in clinical development for treatment of leukemias. P53 can modulate other programmed cell death pathways including autophagy both transcriptionally and non-transcriptionally. We investigated autophagy induction in acute leukemia by Nutlin 3a, a first-in-class MDM2 inhibitor. Nutlin 3a induced autophagy in a p53 dependent manner and transcriptional activation of AMP kinase (AMPK) is critical, as this effect is abrogated in AMPK -/- mouse embryonic fibroblasts. Nutlin 3a induced autophagy appears to be pro-apoptotic as pharmacological (bafilomycin) or genetic inhibition (BECLIN1 knockdown) of autophagy impairs apoptosis induced by Nutlin 3a. |
url |
http://europepmc.org/articles/PMC4595506?pdf=render |
work_keys_str_mv |
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