Intracellular localization of human ZBP1: Differential regulation by the Z-DNA binding domain, Zα, in splice variants

Department of Chemistry, Sungkyunkwan University, Sŏul, Seoul, South Korea
Biochemical and Biophysical Research Communications (Impact Factor: 2.3). 10/2006; 348(1):145-52. DOI: 10.1016/j.bbrc.2006.07.061
Source: PubMed


We investigated the subcellular distribution of human ZBP1, which harbors the N-terminal Z-DNA binding domains, Zalpha and Zbeta. ZBP1 was distributed primarily in the cytoplasm and occasionally as nuclear foci in interferon (IFN)-treated primary hepatocellular carcinoma cells, and in several other transfected cell types. In leptomycin B (LMB)-treated cells, endogenous ZBP1 efficiently accumulated in nuclear foci, which overlapped PML oncogenic domains (PODs) or nuclear bodies (NBs). In transfection assays, the unique C-terminal region of ZBP1 was necessary for its typical cytoplasmic localization. Interestingly, the Zalpha-deleted form displayed an increased association with PODs compared to wild-type and, unlike wild-type, perfectly accumulated in PODs in LMB-treated cells, implying that the presence of Zalpha domain also facilitates the cytoplasmic localization. Our results demonstrate that ZBP1 is localized primarily in the cytoplasm but also associated with nuclear PODs in IFN or LMB-treated cells. Given that about half of ZBP1 mRNA lacks exon 2 encoding the Zalpha domain, our data also suggest that the localization of ZBP1 may be differentially regulated by the Z-DNA binding domain, Zalpha, in splice variants.

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Available from: Thanh Pham, Sep 30, 2015
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    • "In all three proteins two Zα domains are found at the amino-terminus and are separated by a linker that varies in size between 16 and 91 amino acids [19]. In addition, expression of these cellular ZBPs are highly induced upon immunostimulation, and the Zα domains determine the subcellular localization of the proteins [26,31,32]. "
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