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Updated: Jul 16, 2026

Prediction and Validation of Gene Regulatory Elements Activated During Retinoic Acid Induced Embryonic Stem Cell Differentiation
Published on: June 21, 2016
RTP801 is a novel retinoic acid-responsive gene associated with myeloid differentiation
Sigal Gery1, Dorothy J Park, Peter T Vuong
1Division of Hematology/Oncology, UCLA School of Medicine, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA 90048, USA. gerys@cshs.org
Objective:
Retinoids are crucial in the regulation of fundamental cellular processes including terminal differentiation of both normal and malignant myeloid progenitors. The aim of this study was to identify and characterize retinoic acid (RA) target genes.
Methods And Results:
RTP801 is a recently cloned stress response gene that acts as a negative regulator of the mTOR pathway. Here we identified RTP801 as a novel early RA target gene in myeloid cells. RTP801 mRNA levels are induced in acute myeloid leukemia (AML) cell lines during RA-dependent differentiation and are differentially expressed during maturation of normal CD34(+) cells. The myeloid-specific, differentiation-related transcription factor C/EBPepsilon also induces RTP801 expression. Overexpression of RTP801 in the U937 leukemic cells leads to growth inhibition and apoptosis. Conversely, silencing of endogenous RTP801 by shRNA reduces RA-induced differentiation of the U937 cells. Downregulation of RTP801 also abrogates hypoxia-induced inhibition of mTOR in those cells.
Conclusion:
Taken together, our data suggest that RTP801 is an important RA-regulated gene involved in myeloid differentiation, which could represent a therapeutic target in leukemia.
Insights
Retinoic acid (RA) induces the stress gene RTP801 in myeloid cells, impacting differentiation and growth. This RA-regulated gene may offer a new therapeutic target for leukemia.
Area of Science:
- Molecular biology
- Cellular differentiation
- Cancer research
Background:
- Retinoids, including retinoic acid (RA), are vital for regulating cellular processes like myeloid progenitor differentiation.
- Understanding RA target genes is crucial for comprehending normal and malignant myeloid cell development.
Purpose of the Study:
- To identify and characterize novel retinoic acid (RA) target genes in myeloid cells.
- To investigate the role of RTP801 as an RA target gene in acute myeloid leukemia (AML) and normal hematopoiesis.
Main Methods:
- Gene expression analysis of RTP801 in AML cell lines and normal CD34(+) cells treated with RA.
- Investigating the role of C/EBPepsilon in regulating RTP801 expression.
- Functional studies using RTP801 overexpression and shRNA-mediated silencing in U937 cells.
- Assessment of mTOR pathway activity under varying RTP801 and hypoxia conditions.
Main Results:
- RTP801 was identified as a novel, early retinoic acid (RA) target gene in myeloid cells.
- RTP801 mRNA levels increased during RA-induced differentiation of AML cells and normal CD34(+) cells.
- Overexpression of RTP801 inhibited U937 cell growth and induced apoptosis, while silencing RTP801 impaired RA-induced differentiation.
- RTP801 regulates the mTOR pathway, affecting hypoxia-induced inhibition.
Conclusions:
- RTP801 is a significant RA-regulated gene involved in myeloid differentiation.
- RTP801 plays a critical role in both normal and malignant myeloid cell maturation.
- RTP801 represents a potential therapeutic target for leukemia treatment.
More Related Videos
09:49Quantitative Measurement of Relative Retinoic Acid Levels in E8.5 Embryos and Neurosphere Cultures Using the F9 RARE-Lacz Cell-based Reporter Assay
Published on: September 6, 2016
09:04Analysis of Retinoic Acid-induced Neural Differentiation of Mouse Embryonic Stem Cells in Two and Three-dimensional Embryoid Bodies
Published on: April 22, 2017
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