Multiple nuclear localization domains have been identified in nuclear proteins, and they finely control nuclear import and functions of those proteins. ZNF268 is a typical KRAB-containing zinc finger protein (KRAB-ZFP), and previous studies have shown that the KRAB domain reinforces nuclear localization of KRAB-ZFPs by interacting with KAP1. In this study, we find that some of 24 zinc fingers of ZNF268 also possess nuclear localization activity. Results of mutagenesis studies suggest that KRAB and zinc fingers are both necessary, and they function both independently and cooperatively for the nuclear localization of ZNF268. However, the subnuclear targeting activities of KRAB and zinc fingers are different. KRAB targets proteins in nucleoplasm, but not in the nucleolus, which is mediated by interaction with KAP1, while zinc fingers target proteins in the whole nucleus uniformly. The cooperative activities of KAP1-KRAB-zinc fingers result in the precise nucleoplasmic, but not nucleolar localization of KRAB-ZFPs. Our studies reveal a novel mechanism for the subcellular localization of KRAB-ZFPs and may help us to further explore their biological functions.

中文翻译：

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锌指与 KRAB 结构域协同作用，用于含 KRAB 的锌指蛋白的核定位。

已在核蛋白中鉴定出多个核定位域，它们可以精细地控制这些蛋白质的核输入和功能。ZNF268 是典型的含 KRAB 的锌指蛋白 (KRAB-ZFP)，之前的研究表明，KRAB 结构域通过与 KAP1 相互作用增强了 KRAB-ZFPs 的核定位。在这项研究中，我们发现 ZNF268 的 24 个锌指中的一些也具有核定位活性。诱变研究的结果表明 KRAB 和锌指都是必要的，并且它们对于 ZNF268 的核定位既独立又协同起作用。然而，KRAB 和锌指的亚核靶向活性不同。KRAB 靶向核质中的蛋白质，但不在核仁中，这是通过与 KAP1 的相互作用介导的，而锌指则均匀地靶向整个细胞核中的蛋白质。KAP1-KRAB-锌指的协同活动导致 KRAB-ZFP 的精确核质定位，但不是核仁定位。我们的研究揭示了 KRAB-ZFPs 亚细胞定位的新机制，可能有助于我们进一步探索它们的生物学功能。