RTP801 is a novel retinoic acid-responsive gene associated with myeloid differentiation.
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.


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.


CONCLUSIONS
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.
Gery
Sigal
S
Division of Hematology/Oncology, UCLA School of Medicine, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA 90048, USA. gerys@cshs.org
Park
Dorothy J
DJ
Vuong
Peter T
PT
Virk
Renu K
RK
Muller
Claudia I
CI
Hofmann
Wolf-K
WK
Koeffler
H Phillip
HP
D000208:Acute Disease; D017209:Apoptosis; D002454:Cell Differentiation / Q000235:genetics*; D002455:Cell Division; D006098:Granulocytes / Q000166:cytology; D006801:Humans; D007951:Leukemia, Myeloid / Q000235:genetics / Q000473:pathology*; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D058570:TOR Serine-Threonine Kinases; D014157:Transcription Factors / Q000235:genetics*; D020298:U937 Cells
C469991:DDIT4 protein, human; D012333:RNA, Messenger; D014157:Transcription Factors; D011494:Protein Kinases; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases