ArticleLeukemia2012
p38αMAPK interacts with and inhibits RARα: suppression of the kinase enhances the therapeutic activity of retinoids in acute myeloid leukemia cells.
Article in Leukemia, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
12 citing papers in PubMed, 24 citations in OpenAlex.
- Role of mitochondria and cardiolipins in growth inhibition of breast cancer cells by retinoic acid.Journal of experimental & clinical cancer research : CR · 2019Article
- Article
- Differentiation therapy revisited.Nature reviews. Cancer · 2018Review
- The autophagy scaffold protein ALFY is critical for the granulocytic differentiation of AML cells.Scientific reports · 2017Article
- RARα2 and PML-RAR similarities in the control of basal and retinoic acid induced myeloid maturation of acute myeloid leukemia cells.Oncotarget · 2017Article
- NLS-RARα Inhibits the Effects of All-trans Retinoic Acid on NB4 Cells by Interacting with P38α MAPK.International journal of medical sciences · 2016Article
- An ATRActive future for differentiation therapy in AML.Blood reviews · 2015Article
- Cellular and molecular determinants of all-trans retinoic acid sensitivity in breast cancer: Luminal phenotype and RARα expression.EMBO molecular medicine · 2015Article
- Catechins induced acute promyelocytic leukemia cell apoptosis and triggered PML-RARα oncoprotein degradation.Journal of hematology & oncology · 2014Article
- E2F1 impairs all-trans retinoic acid-induced osteogenic differentiation of osteosarcoma via promoting ubiquitination-mediated degradation of RARα.Cell cycle (Georgetown, Tex.) · 2014Article
- Differential effects of retinoids and inhibitors of ERK and p38 signaling on adipogenic and myogenic differentiation of P19 stem cells.Stem cells and development · 2013Article
- Retinoids augment the expression of podocyte proteins by glomerular parietal epithelial cells in experimental glomerular disease.Nephron. Experimental nephrology · 2012Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
All-trans retinoic acid (ATRA) is the only clinically useful differentiating agent, being used in the treatment of acute promyelocytic leukemia (APL). The use of ATRA in other types of acute myelogenous leukemia (AML) calls for the identification of novel strategies aimed at increasing its therapeutic activity. Here, we provide evidence that pharmacological inhibition of the mitogen-activated protein kinase, p38α, or silencing of the corresponding gene sensitizes APL and AML cell lines, as well as primary cultures of AML blasts to the anti-proliferative and cyto-differentiating activity of ATRA and synthetic retinoids. P38α inhibits ligand-dependent transactivation of the nuclear retinoic acid receptor, RARα, and the derived chimeric protein expressed in the majority of APL cases, PML-RARα. Inhibition is the consequence of ligand-independent binding of p38α, which results in stabilization of RARα and PML-RARα via blockade of their constitutive degradation by the proteasome. The inhibitory effect requires a catalytically active p38α and direct physical interaction with RARα and PML-RARα. Ser-369 in the E-region of RARα is essential for the binding of p38α and the ensuing functional effects on the activity of the receptor.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.