Xie J, Briggs J A, Morris S W, Olson M O, Kinney M C, Briggs R C
Department of Pathology, Vanderbilt University School of Medicine, Nashville, TN 37232-5310, USA.
Exp Hematol. 1997 Oct;25(11):1111-7.
The myeloid cell nuclear differentiation antigen (MNDA) is a nuclear protein expressed specifically in developing cells of the human myelomonocytic lineage, including the end-stage monocytes/macrophages and granulocytes. Nuclear localization, lineage- and stage-specific expression, association with chromatin, and regulation by interferon alpha indicate that this protein is involved in regulating gene expression uniquely associated with the differentiation process and/or function of the monocyte/macrophage. MNDA does not bind specific DNA sequences, but rather a set of nuclear proteins that includes nucleolin (C23). Both in vitro binding assays and co-immunoprecipitation were used to demonstrate that MNDA also binds protein B23 (nucleophosmin/NPM). Three reciprocal chromosome translocations found in certain cases of leukemia/lymphoma involve fusions with the NPM/B23 gene, t(5;17) NPM-RARalpha, t(2;5) NPM-ALK, and the t(3;5) NPM-MLF1. In the current study, MNDA was not able to bind the NPM-ALK chimera originating from the t(2;5) and containing residues 1-117 of NPM. However, MNDA did bind the NPM-MLF1 product of the t(3;5) that contains the N-terminal 175 residues of NPM. The additional 58 amino acids (amino acids 117-175) of the NPM sequence that are contained in the product of the NPM-MLF1 fusion gene relative to the product of the NPM-ALK fusion appear responsible for MNDA binding. This additional NPM sequence contains a nuclear localization signal and clusters of acidic residues believed to bind nuclear localization signals of other proteins. Whereas NPM and nucleolin are primarily localized within the nucleolus, MNDA is distributed throughout the nucleus including the nucleolus, suggesting that additional interactions define overall MNDA localization.
髓系细胞核分化抗原（MNDA）是一种核蛋白，在人类髓单核细胞系的发育细胞中特异性表达，包括终末阶段的单核细胞/巨噬细胞和粒细胞。核定位、谱系和阶段特异性表达、与染色质的关联以及受α干扰素调节表明，该蛋白参与调控与单核细胞/巨噬细胞分化过程和/或功能独特相关的基因表达。MNDA不结合特定的DNA序列，而是结合一组包括核仁素（C23）的核蛋白。体外结合试验和免疫共沉淀均用于证明MNDA也结合蛋白B23（核磷蛋白/NPM）。在某些白血病/淋巴瘤病例中发现的三种相互的染色体易位涉及与NPM/B23基因的融合，即t(5;17) NPM-RARα, t(2;5) NPM-ALK, 以及t(3;5) NPM-MLF1。在本研究中，MNDA无法结合源自t(2;5)且包含NPM第1至117位残基的NPM-ALK嵌合体。然而，MNDA确实结合了t(3;5)的NPM-MLF1产物，该产物包含NPM的N端175个残基。相对于NPM-ALK融合产物，NPM-MLF1融合基因产物中所含的NPM序列额外的58个氨基酸（第117至175位氨基酸）似乎是MNDA结合所必需的。该额外的NPM序列包含一个核定位信号以及据信可结合其他蛋白核定位信号的酸性残基簇。虽然NPM和核仁素主要定位于核仁内，但MNDA分布于整个细胞核包括核仁，这表明其他相互作用决定了MNDA的整体定位。
