Le X F, Groner Y, Kornblau S M, Gu Y, Hittelman W N, Levanon D, Mehta K, Arlinghaus R B, Chang K S
Division of Pathology and Laboratory Medicine, the University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
J Biol Chem. 1999 Jul 30;274(31):21651-8. doi: 10.1074/jbc.274.31.21651.
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) alpha nor retinoic X receptor alpha 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 RARalpha 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 AML2 in HL-60 cells is regulated through the RARalpha-specific signaling pathway. Our study further showed that after all-trans-retinoic acid priming, AML2 expression could be augmented by vitamin D(3). Based on these studies we hypothesize that AML2 expression is normally regulated by retinoid/vitamin D nuclear receptors mainly through the RARalpha-dependent signaling pathway and that it may play a role in hematopoietic cell differentiation.
AML2是急性髓性白血病转录因子AML家族的成员。AML1和AML3的生物学功能已得到充分表征；然而，AML2的功能作用仍不清楚。在本研究中，我们发现主要在造血来源细胞中表达的AML2蛋白是一种与核基质相关的核丝氨酸磷酸蛋白，其表达与细胞周期无关。在HL-60细胞中，AML2的表达可被三种天然维甲酸全反式维甲酸（RA）、13-顺式维甲酸和9-顺式维甲酸以剂量依赖的方式诱导。一种既不激活RA受体（RAR）α也不激活维甲酸X受体α的合成维甲酸衍生物4HPR不能诱导AML2的表达。一种RAR选择性激活剂TTNPB诱导AML2表达的情况与RA相似。我们的研究进一步表明，一种有效的RARα拮抗剂AGN193109可抑制RA诱导的AML2表达，而一种维甲酸X受体泛激动剂AGN194204对其表达没有影响。综上所述，这些研究确凿地证明HL-60细胞中AML2的表达是通过RARα特异性信号通路调节的。我们的研究进一步表明，在全反式维甲酸预处理后，维生素D(3)可增强AML2的表达。基于这些研究，我们推测AML2的表达通常由类维生素A/维生素D核受体主要通过RARα依赖性信号通路调节，并且它可能在造血细胞分化中起作用。
