Zinc fingers 1, 2, 5 and 6 of transcriptional regulator, PRDM4, are required for its nuclear localisation.

Zinc fingers 1, 2, 5 and 6 of transcriptional regulator, PRDM4, are required for its nuclear localisation.
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转录调节因子 PRDM4 的锌指 1、2、5 和 6 是其核定位所必需的。

DOI:
10.1016/j.bbrc.2016.04.128
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发表时间:
2016
影响因子:
3.1
通讯作者:
Tunbak H
Tunbak H
中科院分区:
生物学4区
文献类型:
--
作者:
Tunbak H

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PRDM 4是控制细胞分化和增殖的各个方面的转录调节因子的PRDM家族的成员。PRDM蛋白在细胞质溶胶和细胞核中发挥其生物学功能。所有PRDM蛋白的特征在于存在两个不同的结构基序,PR/SET结构域和锌指(ZF)基序。我们先前观察到PRDM 4中发现的所有六个锌指的缺失导致其在细胞质中的积累,而过表达的全长PRDM 4主要在细胞核中发现。在这里,我们研究了在PRDM 4的核定位中对单个锌指的要求。我们证明ZF的1,2,5和6有助于PRDM 4在细胞核中的积累。它们的作用是累加的,因为缺失ZF 1 -2或ZF 5-6将PRDM 4蛋白从几乎仅在核中重新分布到胞质和核中。我们研究了PRDM 4通过importin α/β介导的途径进行核穿梭的潜在机制,发现PRDM 4核靶向不依赖于α/β介导的核输入。
PRDM4 is a member of the PRDM family of transcriptional regulators which control various aspects of cellular differentiation and proliferation. PRDM proteins exert their biological functions both in the cytosol and the nucleus of cells. All PRDM proteins are characterised by the presence of two distinct structural motifs, the PR/SET domain and the zinc finger (ZF) motifs. We previously observed that deletion of all six zinc fingers found in PRDM4 leads to its accumulation in the cytosol, whereas overexpressed full length PRDM4 is found predominantly in the nucleus. Here, we investigated the requirements for single zinc fingers in the nuclear localisation of PRDM4. We demonstrate that ZF's 1, 2, 5 and 6 contribute to the accumulation of PRDM4 in the nucleus. Their effect is additive as deleting either ZF1-2 or ZF 5–6 redistributes PRDM4 protein from being almost exclusively nuclear to cytosolic and nuclear. We investigated the potential mechanism of nuclear shuttling of PRDM4 via the importin α/β-mediated pathway and find that PRDM4 nuclear targeting is independent of α/β-mediated nuclear import.
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