The highly conserved region within exonuclease III-like in PML-I regulates the cytoplasmic localization of PML-NBs.

IF 4 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Biological Chemistry Pub Date : 2024-10-10 DOI:10.1016/j.jbc.2024.107872

Xinxin Liang,Jinwen Chen,Peijie Yan,Zhongzhou Chen,Chao Gao,Rulan Bai,Jun Tang

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引用次数: 0

Abstract

The sub-nuclear protein structure PML-NB regulates a wide range of important cellular functions, while its abnormal cytoplasmic localization may have pathological consequences. However, the nature of this aberrant localization remains poorly understood. In this study, we unveil that PML-I, the most conserved and abundant structural protein of PML-NB, possesses potent cytoplasmic targeting ability within the N-terminal half of the exonuclease III-like domain encoded by its unique exon 9, independent of the known nuclear localization signal. Fusion of this region to PML-VI can relocate PML-VI from the nucleus to the cytosol. Structural and deletion analysis revealed that the cytoplasmic targeting ability of this domain was restrained by the sequences encoded by exon 8a and the 3' portion of exon 9 in PML-I. Deletion of either of these regions relocates PML-I to the cytosol. Furthermore, we observed a potential interaction between the ER-localized TREX1 and the cytoplasmic-located PML-I mutants. Our results suggest that perturbation of the EXO-like domain of PML-I may represent an important mode to translocate PMLs from the nucleus to the cytosol, thereby interfering with the normal nuclear functions of PML-NBs.

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PML-I 中类似于 III 号外切酶的高度保守区域调节 PML-NBs 的细胞质定位。

核下蛋白结构 PML-NB 可调节多种重要的细胞功能，而其异常的细胞质定位可能会产生病理后果。然而，人们对这种异常定位的本质仍然知之甚少。在这项研究中，我们发现 PML-I 是 PML-NB 中最保守、最丰富的结构蛋白，在其独特的外显子 9 所编码的类似外切酶 III 结构域的 N 端半部分具有强大的胞浆靶向能力，与已知的核定位信号无关。将该区域与 PML-VI 融合可将 PML-VI 从细胞核移至细胞质。结构和缺失分析表明，该结构域的细胞质靶向能力受到 PML-I 中外显子 8a 和外显子 9 3' 部分编码序列的限制。缺失这两个区域中的任何一个都会使 PML-I 转移到细胞质中。此外，我们还观察到定位在 ER 的 TREX1 与定位在细胞质的 PML-I 突变体之间可能存在相互作用。我们的研究结果表明，PML-I的EXO样结构域的扰动可能是将PML从细胞核转位到细胞质的一种重要模式，从而干扰了PML-NB的正常核功能。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Biological Chemistry Biochemistry, Genetics and Molecular Biology-Biochemistry

自引率

4.20%

发文量

1233

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