Zhong H, Dong S, Chen G, Jiang X, Xia Z, Yi N, Wang Z, Chen S, Xu Y, Chen L
Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Second Medical University, Shanghai 200025.
Zhonghua Xue Ye Xue Za Zhi. 1997 Jul;18(7):339-42.
To make a comparison of biological properties between PML-RARalpha and PLZF-RARalpha fusion proteins.
Receptor radioligand binding assay, receptor DNA binding assay and immunofluorescence methods were used.
PML-RARalpha and PLZF-RARalpha had similar ligand-binding affinities. Both could bind in vitro to retinoic acid response elements (RAREs) forming homodimers and to retinoic acid X receptor. However ,they differed in the relative binding affinities to different RAREs,the behavior of forming complex with RXR and the subcellular localization. More importantly, PML-RARalpha and PLZF-RARalpha could block different regulatory pathways mediated by PML or PLZF, through heterocomplex formation with wild-type PML or PLZF. The differences between PML-RARalpha and PLZF-RARalpha may in part explain the apparent resistance of APL with t(11;17) to differentiating effect of all-trans retinoic acid (ATRA).
比较早幼粒细胞白血病/维甲酸受体α（PML-RARα）和早幼粒细胞白血病锌指蛋白/维甲酸受体α（PLZF-RARα）融合蛋白的生物学特性。
采用受体放射性配体结合分析、受体DNA结合分析及免疫荧光法。
PML-RARα和PLZF-RARα具有相似的配体结合亲和力。二者均可在体外与形成同二聚体的维甲酸反应元件（RAREs）结合，并与维甲酸X受体结合。然而，它们在对不同RAREs的相对结合亲和力、与维甲酸X受体形成复合物的行为及亚细胞定位方面存在差异。更重要的是，PML-RARα和PLZF-RARα可通过与野生型PML或PLZF形成异源复合物，阻断由PML或PLZF介导的不同调控途径。PML-RARα和PLZF-RARα之间的差异可能部分解释了伴有t(11;17)的急性早幼粒细胞白血病（APL）对全反式维甲酸（ATRA）分化作用明显耐药性的原因。
