Lavau C, Jansen J, Dejean A
Dept des Rétrovirus, INSERM U. 163, Institut Pasteur, Paris, France.
Pathol Biol (Paris). 1995 Mar;43(3):188-96.
Retinoic acid (RA) is a vitamin A derivative with striking effects on development and cell differentiation. The identification of three RA receptors (RAR alpha, beta and gamma) as members of the nuclear receptor superfamily led to important insights into the molecular mechanism of action of retinoids. The nuclear receptors, that also include receptors for steroid hormone, vitamin D3 and thyroid hormone act as ligand-inducible transcription factors and are characterized by the presence of two well conserved DNA- and hormone-binding domains. One of the most intriguing properties of RA is its ability to induce in vivo differentiation of acute promyelocytic leukaemia (APL) cells into mature granulocytes, leading to morphological complete remissions. We and others have shown that the t(15;17) translocation specifically associated with APL fuses an as yet unidentified gene, named PML, to the retinoic acid receptor alpha locus. The resulting PML-RAR alpha hybrid protein that retains most of the functional domains of parental proteins exhibits altered transactivating functions when compared to the wild-type receptor; however the biological significance of this property in the transforming phenotype is still obscure. PML, whose function is unknown, belongs to a novel family of nuclear proteins characterized by the presence of a Cys/His-rich motif, named a RING finger, that include RNA-binding proteins, transcription factors and oncoproteins. A dimerization domain within PML is able to mediate the formation of PML-RAR alpha homodimers that can bind to target sequences with distinct DNA binding properties if compared with RAR alpha.(ABSTRACT TRUNCATED AT 250 WORDS)
维甲酸（RA）是一种维生素A衍生物，对发育和细胞分化具有显著影响。三种RA受体（RARα、β和γ）被鉴定为核受体超家族成员，这为深入了解类视黄醇的分子作用机制提供了重要线索。核受体还包括类固醇激素、维生素D3和甲状腺激素的受体，它们作为配体诱导型转录因子，其特征是存在两个高度保守的DNA结合域和激素结合域。RA最引人注目的特性之一是它能够在体内诱导急性早幼粒细胞白血病（APL）细胞分化为成熟粒细胞，从而导致形态学上的完全缓解。我们和其他人已经表明，与APL特异性相关的t(15;17)易位将一个尚未确定的基因（称为PML）与维甲酸受体α基因座融合。产生的PML-RARα融合蛋白保留了亲本蛋白的大部分功能域，与野生型受体相比，其反式激活功能发生了改变；然而，这种特性在转化表型中的生物学意义仍不清楚。PML的功能未知，它属于一个新的核蛋白家族，其特征是存在一个富含半胱氨酸/组氨酸的基序，称为环指结构，该家族包括RNA结合蛋白、转录因子和癌蛋白。PML内的二聚化结构域能够介导PML-RARα同二聚体的形成，与RARα相比，该同二聚体能够以不同的DNA结合特性结合靶序列。（摘要截断于250字）
