TY - JOUR
T1 - Regulation of AML2/CBFA3 in hematopoietic cells through the retinoic acid receptor α-dependent signaling pathway
AU - Le, Xiao Feng
AU - Groner, Yoram
AU - Kornblau, Steve M.
AU - Gu, Yun
AU - Hittelman, Walter N.
AU - Levanon, Ditsa
AU - Mehta, Kapil
AU - Arlinghaus, Ralph B.
AU - Chang, Kun Sang
PY - 1999/7/30
Y1 - 1999/7/30
N2 - AML2 is a member of the acute myelogenous leukemia, AML family of transcription factors. The biologic functions of AML1 and AML3 have been well characterized; however, the functional role of AML2 remains unknown. In this study, we found that AML2 protein expressed predominantly in cells of hematopoietic origin is a nuclear serine phosphoprotein associated with the nuclear matrix, and its expression is not cell cycle-related. In HL-60 cells AML2 expression can be induced by all three natural retinoids, all-trans- retinoic acid (RA), 13-cis-RA, and 9-cis-RA in a dose-dependent manner. A synthetic retinoic acid derivative, 4HPR, which neither activates RA receptor (RAR) α nor retinoic X receptor was unable to induce the expression of AML2. A RAR-selective activator, TTNPB, induced AML2 expression similar to RA. Our study further showed that AGN193109, a potent RARα antagonist, suppressed AML2 expression induced by RA and that a retinoic X receptor pan agonist AGN194204 had no effect on its expression. Taken together, these studies conclusively demonstrated that the expression of ML2 in HL-60 cells is regulated through the RARα-specific signaling pathway. Our study further showed that after all-trans-retinoic acid priming, AML2 expression could be augmented by vitamin D3. Based on these studies we hypothesize that AML2 expression is normally regulated by retinoid/vitamin D nuclear receptors mainly through the RARα-dependent signaling pathway and that it may play a role in hematopoietic cell differentiation.
AB - AML2 is a member of the acute myelogenous leukemia, AML family of transcription factors. The biologic functions of AML1 and AML3 have been well characterized; however, the functional role of AML2 remains unknown. In this study, we found that AML2 protein expressed predominantly in cells of hematopoietic origin is a nuclear serine phosphoprotein associated with the nuclear matrix, and its expression is not cell cycle-related. In HL-60 cells AML2 expression can be induced by all three natural retinoids, all-trans- retinoic acid (RA), 13-cis-RA, and 9-cis-RA in a dose-dependent manner. A synthetic retinoic acid derivative, 4HPR, which neither activates RA receptor (RAR) α nor retinoic X receptor was unable to induce the expression of AML2. A RAR-selective activator, TTNPB, induced AML2 expression similar to RA. Our study further showed that AGN193109, a potent RARα antagonist, suppressed AML2 expression induced by RA and that a retinoic X receptor pan agonist AGN194204 had no effect on its expression. Taken together, these studies conclusively demonstrated that the expression of ML2 in HL-60 cells is regulated through the RARα-specific signaling pathway. Our study further showed that after all-trans-retinoic acid priming, AML2 expression could be augmented by vitamin D3. Based on these studies we hypothesize that AML2 expression is normally regulated by retinoid/vitamin D nuclear receptors mainly through the RARα-dependent signaling pathway and that it may play a role in hematopoietic cell differentiation.
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U2 - 10.1074/jbc.274.31.21651
DO - 10.1074/jbc.274.31.21651
M3 - Article
C2 - 10419474
AN - SCOPUS:0033618306
SN - 0021-9258
VL - 274
SP - 21651
EP - 21658
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 31
ER -