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目的:就配基-受体、受体-DNA和蛋白质-蛋白质相互作用,以及蛋白质的亚细胞定位等方面,对早幼粒细胞白血病-维甲酸受体α(PML-RARα)与早幼粒细胞白血病锌指-维甲酸受体α(PLZF-RARα)融合蛋白的生物学功能进行比较。方法:采用受体放射配基结合分析、受体-DNA结合分析及免疫荧光技术。结果和结论:PML-RARα与PLZF-RARα融合蛋白有相似的配基结合亲和力;两者都能以同二聚体形式结合维甲酸反应元件(RAREs);都能与维甲类X受体(RXR)结合,提示PML-RARα和PLZF-RARα在急性早幼粒细胞白血病(APL)的发病中有共同的分子基础。但是,两者在某些特性方面又有所不同,如:PML-RARα和PLZF-RARα结合RAREs的相对强度有所差异;两者在与RXR形成复合物的行为以及亚细胞定位方面亦不尽相同;尤为重要的是,两者可分别通过与PML和PLZF形成异源复合物而阻断PML和PLZF蛋白质所介导的不同调节途径。因此,PML-RARα与PLZF-RARα之间的这些差异,可能部分解释伴t(11;17)的APL患者对全反式维甲酸诱导分化治疗耐药的原因。
OBJECTIVE: To investigate the roles of ligand-receptor, receptor-DNA and protein-protein interactions, and the subcellular localization of proteins in the promyelocytic leukemia-retinoid receptor alpha (PML-RARα) and promyelocytic leukemia The biological function of the cell leukemia zinc finger-retinoid receptor alpha (PLZF-RARα) fusion protein was compared. METHODS: Receptor radioligand binding assays, receptor-DNA binding assays, and immunofluorescence techniques were used. RESULTS AND CONCLUSION: PML-RARα and PLZF-RARα fusion proteins have similar ligand binding affinities; both can bind the retinoid acid response elements (RAREs) as homodimers; both can interact with retinoid X receptors ( RXR) binding suggests that PML-RARα and PLZF-RARα share a common molecular basis in the pathogenesis of acute promyelocytic leukemia (APL). However, the two are different in some characteristics, such as: PML-RARα and PLZF-RARα combined RAREs have different relative intensities; both in the formation of complexes with RXR behavior and subcellular localization are also not exhaustive The same; more importantly, both can block the different regulatory pathways mediated by PML and PLZF proteins by forming heterologous complexes with PML and PLZF, respectively. Therefore, these differences between PML-RARα and PLZF-RARα may partially account for the causes of resistance to all-trans retinoic acid-induced differentiation in APL patients with t(11;17).