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Query: UNIPROT:P06889 (Mol)
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The advancement in gene knockout and transgenesis have brought about enormous improvement in our understanding of mouse embryogenesis in the past decade or so. On the other hand, relatively little is known about human embryogenesis due largely to the lack of easy access to human embryos and tissues for biomedical studies. We have previously isolated a novel zinc finger gene, ZNF268, from a 3-week-old human embryo cDNA library in an effort to identify genes important for human embryonic development. To investigate the potential involvement of ZNF268 in human embryogenesis, we report here the spatial and temporal regulation of its expression during development. Northern blot and Western blot analyses revealed that ZNF268 is expressed in early embryos, predominantly, if not exclusively, in fetal liver with little detectable expression in other fetal organs. Interestingly, unlike most zinc finger proteins, ZNF268 protein was found to be localized mainly in the cytoplasm of embryonic hepatocytes. This subcellular localization was substantiated by the localization of EGFP-ZNF268 fusion protein overexpressed in the transfected COS7 cells. These results suggest that ZNF268 plays a role in early human liver development most likely by functioning through a cytoplasmic mechanism.
Int J Mol Med 2004 Dec
PMID:ZNF268, a novel kruppel-like zinc finger protein, is implicated in early human liver development. 1554 61

The ZNF268 gene was originally isolated from an early human embryo cDNA library. Several different transcripts have been isolated for the ZNF268 gene and developmental expression studies suggest that ZNF268 plays a role in the development of human fetal liver and the differentiation of blood cells. In our effort to study the functions of ZNF268 in different organs during development and in pathogenesis, we have now identified 3 novel splicing isoforms, ZNF268e, ZNF268f and ZNF268g, in human fetal tissues and human tumor derived cell lines. The 8 alternatively spliced mRNAs discovered so for are predicted to encode 3 protein isoforms. Expression analysis showed that different mRNA isoforms have different expression profiles. In particular, ZNF268c mRNA was detected only in tumor cells, and ZNF268f appeared to be tissue-specific. By Western blot analysis, all 3 ZNF268 protein isoforms, ZNF268a, ZNF268b1 and ZNF268b2, were expressed in tumor cell lines, while only two protein products, ZNF268b1 and ZNF268b2, were detected in human fetal tissues. Subcellular localization analysis showed that ZNF268a and ZNF268b2 distributed diffusely throughout the cell, while ZNF268b1 mainly localized in the cytoplasm. Moreover, using a CAT reporter system fused to the Gal4 DNA binding domain of the ZNF268 gene, the ZNF268a and b2 activated the CAT reporter gene expression, while the KRAB domain, corresponding to the ZNF268b1 repressed the reporter gene expression. Taken together, our results showed that multiple ZNF268 splicing products encode multiple ZNF268 protein isoforms with different subcellular localization, and that the ZNF268 gene may function as a transcriptional activator in the growth and differentiation of cells in development and/or pathogenesis.
Int J Mol Med 2006 Sep
PMID:KRAB-containing zinc finger gene ZNF268 encodes multiple alternatively spliced isoforms that contain transcription regulatory domains. 1686 30

IkappaB kinase (IKK), the pivotal kinase in signal-dependent activation of nuclear factor-kappaB (NF-kappaB), is composed of multiple protein components, including IKK alpha/beta/gamma core subunits. To investigate the regulation of the IKK complex, we immunoaffinity purified the IKK complex, and by MALDI-TOF mass spectrometry identified a splice variant of zinc finger protein 268 (ZNF268) as a novel IKK-interacting protein. Both the full-length and the spliced form of the ZNF268 protein were detected in a variety of mammalian tissues and cell lines. The genes were cloned and expressed by in vitro transcription/translation. Several deletion derivatives, such as KRAB domain (KRAB) on its own, the KRAB/spacer/4-zinc fingers (zF4), and the spacer/ 4-zinc fingers (zS4), were ectopically expressed in mammalian cells and exhibited had different subcellular locations. The KRAB-containing mutants were restricted to the nucleus, while zS4 was localized in the cytosol. TNF-alpha-induced NF-kappaB activation was examined using these mutants and only zS4 was found to stimulate activation. Collectively, the results indicate that a spliced form of ZNF268 lacking the KRAB domain is located in the cytosol, where it seems to play a role in TNF-alpha-induced NF-kappaB activation by interacting with the IKK complex.
Mol Cells 2008 Aug 31
PMID:A splice variant of the C(2)H(2)-type zinc finger protein, ZNF268s, regulates NF-kappaB activation by TNF-alpha. 1867 94