Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:Q9UID6 (Kruppel-like)
 147 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The ZNF219 gene is a member of the Kruppel-like zinc finger gene family that is involved in a diverse range of biological processes. The ZNF219 gene encodes a 77-kDa nuclear protein containing nine sets of C2H2 zinc finger structures. By using a random oligonucleotide selection assay and the electromobility gel shift assay, we have revealed that the ZNF219 protein recognizes two copies of CCCCCA. The DNA binding core element is CCCCC. 3' flanking A residues enhance binding of the ZNF219 protein. Use of the various truncated ZNF219 constructs demonstrated that zinc finger 1 to 3 or zinc finger 5 and 6 domains are sufficient to allow specific DNA binding. Both domains independently recognized the same consensus sequence, CCCCCA. Proteins expressed from human cDNA clones KIAA0390 and KIAA0222, which have partial similarities to ZNF219, also showed specific binding to the same core DNA sequence. Potential ZNF219 binding sites were found in the HMGN1 promoter. To examine the function of ZNF219 in the modulation of transcription, we constructed Gal4 DNA binding domain (DBD)/ZNF219 fusion proteins and demonstrated that ZNF219 functioned as a transcriptional repressor for the HMGN1 promoter. Experiments with the truncated ZNF219 constructs suggest that the proline-rich sequence (226-272 a.a., proline content 49%) was responsible for part of the observed repression. These findings provide us with an important start point in our understanding of the functional role of ZNF219 in vivo.
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PMID:Identification of the DNA binding specificity of the human ZNF219 protein and its function as a transcriptional repressor. 1462 Dec 94

Activation of hepatic stellate cells (HSCs) is the central event in the development of liver fibrosis and cirrhosis. The transdifferentiation process of quiescent into activated HSCs requires a complete reprogramming in gene expression, which is governed by modulation of transcriptional activators or repressors. Using microarray analysis to identify genes differentially expressed during the activation process of human HSCs, zinc finger protein 267 (ZNF267) mRNA was up-regulated in activated HSCs and in cirrhotic human liver. ZNF267 belongs to the family of Kruppel-like zinc fingers and contains a conserved KRAB (Kruppel associated box) A and B domain in the N-terminal part outside the C-terminal region of zinc fingers. ZNF267 constructs containing enhanced cyan fluorescence protein were constitutively localized in the nucleus. When fused to GAL4 DNA binding domain, full-length ZNF267 and all constructs encompassing KRAB A domain showed transcriptional repressor activity. Microarray analysis and RNase protection assays showed that ZNF267 represses MMP-10 gene expression, which was confirmed by reporter gene assays. Furthermore, ZNF267 binds to the MMP-10 promoter region as demonstrated by chromatin immunoprecipitation assays. In conclusion, our results suggest that ZNF267 as a negative transcriptional regulator of MMP-10 might promote liver fibrogenesis through alteration of matrix degradation in vivo.
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PMID:Zinc finger protein 267 is up-regulated during the activation process of human hepatic stellate cells and functions as a negative transcriptional regulator of MMP-10. 1605 93

Alpha-catenins anchor the transmembrane cell-cell adhesion molecule E-cadherin indirectly to the actin cytoskeleton through interaction with beta-catenin or plakoglobin. Three different alpha-catenins are known at present: alphaE-, alphaT-, and alphaN-catenin. Despite their different expression patterns, no functional differences between the alpha-catenins are known. In a yeast two-hybrid screening with alphaN-catenin as bait, we identified the Cys(2)-His2 zinc finger protein ZASC1. The mRNA and protein of ZASC1 were ubiquitously expressed in various cell lines and human tissues. Our results suggest an association of the ZASC1 protein with DNA, and luciferase reporter assays revealed that ZASC1 is a transcriptional repressor. Upon transient overexpression, the ZASC1 protein localized in the nucleus, to where it was able to recruit cytoplasmic alphaN-catenin. Neither the highly related alphaE-catenin nor alphaT-catenin interacted with ZASC1. By interchanging parts of alphaN-catenin and alphaE-catenin cDNAs, we were able to narrow down the interaction region of alphaN-catenin to two limited amino-terminal regions. On the other hand, the interaction of ZASC1 with alphaN-catenin can be mediated by the domain comprising zinc fingers six to eight of ZASC1. The interaction and nuclear cotranslocation of a neural alpha-catenin with a putative proto-oncogene product as reported here provides novel insights into the signaling functions of alpha-catenins.
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PMID:Nuclear translocation of alphaN-catenin by the novel zinc finger transcriptional repressor ZASC1. 1618 84

Zinc-finger protein 217 (ZNF217) is a Kruppel-like zinc-finger protein located at 20q13.2, within a region of recurrent maximal amplification. Here, we demonstrate that ZNF217 is a transcriptional repressor protein and report the purification and characterization of a ZNF217 complex. The purified ZNF217 complex consists of approximately six proteins and contains the transcriptional co-repressors CoREST, BHC110/LSD1, histone deacetylase (HDAC) 2 and C-terminal binding protein (CtBP1). The purified ZNF217 complex possesses deacetylase activity as well as lysine 4 histone H3-specific demethylase activity that is most likely mediated by the BHC110/LSD1 component. To determine if ZNF217 is a sequence-specific binding protein, we have made use of cyclic amplification and selection of targets (CAST) assay and identify for the first time a ZNF217 DNA consensus recognition sequence (CRS) that is highly conserved in the human E-cadherin promoter. Chromatin immunoprecipitation (ChIP) experiments demonstrate that ZNF217, as well as the other components of the ZNF217 complex, are found on the region of the proximal E-cadherin promoter that contains the identified ZNF217 CRS in vivo. Using a combination of transient transfections and small interfering RNA, we demonstrate that ZNF217 represses the E-cadherin promoter. Collectively, our results implicate ZNF217 and its associated proteins in a novel pathway that may have profound effects on cancer progression.
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PMID:Biochemical characterization of the zinc-finger protein 217 transcriptional repressor complex: identification of a ZNF217 consensus recognition sequence. 1713 Aug 29

The Tax protein encoded by human T-cell leukaemia virus type 1 (HTLV-1) has a pivotal role in T-cell transformation by deregulating cellular signalling pathways. Using the yeast two-hybrid system to screen a human leukocyte cDNA library, we identified BCL6 (B-cell lymphoma 6) as a cellular protein, which interacts with Tax 1. The BCL6 gene encodes a sequence-specific transcriptional repressor that contains a conserved N-terminal poxvirus and zinc finger (POZ) repressor domain and a C-terminal Kruppel-like zinc finger DNA binding domain. Using both in vivo and in vitro methods, we demonstrate that the POZ domain of BCL6 is sufficient for its interaction with Tax 1. Using functional assays, we demonstrate that Tax 1 enhanced the repressive activity of BCL6 and increased the levels of apoptosis induced by BCL6 in osteosarcoma cells indicating that both proteins cooperate in vivo to cause a physiological affect. Furthermore, BCL6 recruited Tax 1 into punctate nuclear structures, which suggests that Tax 1 colocalizes with BCL6 in repressor complexes in vivo. BCL6 expression significantly downregulated both basal and Tax-induced nuclear factor-kappaB and long terminal repeat activation. This suggests that the expression of BCL6 in HTLV infected cells may contribute to the silencing of viral gene expression and to the long clinical latency associated with HTLV infection.
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PMID:Functional interaction of HTLV-1 tax protein with the POZ domain of the transcriptional repressor BCL6. 1970 Dec 48