scholarly journals Structures and biological functions of zinc finger proteins and their roles in hepatocellular carcinoma

2022 ◽  
Vol 10 (1) ◽  
Author(s):  
Xinxin Li ◽  
Mengzhen Han ◽  
Hongwei Zhang ◽  
Furong Liu ◽  
Yonglong Pan ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Transcription Factors ◽  
Zinc Finger ◽  
Zinc Finger Proteins ◽  
Biological Functions ◽  
Binding Motifs ◽  
Zinc Finger Motifs ◽  
Tumorigenesis And Progression ◽  
Long Time ◽  
Underlying Mechanisms

AbstractZinc finger proteins are transcription factors with the finger domain, which plays a significant role in gene regulation. As the largest family of transcription factors in the human genome, zinc finger (ZNF) proteins are characterized by their different DNA binding motifs, such as C2H2 and Gag knuckle. Different kinds of zinc finger motifs exhibit a wide variety of biological functions. Zinc finger proteins have been reported in various diseases, especially in several cancers. Hepatocellular carcinoma (HCC) is the third leading cause of cancer-associated death worldwide, especially in China. Most of HCC patients have suffered from hepatitis B virus (HBV) and hepatitis C virus (HCV) injection for a long time. Although the surgical operation of HCC has been extremely developed, the prognosis of HCC is still very poor, and the underlying mechanisms in HCC tumorigenesis are still not completely understood. Here, we summarize multiple functions and recent research of zinc finger proteins in HCC tumorigenesis and progression. We also discuss the significance of zinc finger proteins in HCC diagnosis and prognostic evaluation.

Single zinc-finger extension: enhancing transcriptional activity and specificity of three-zinc-finger proteins

2005 ◽  
Vol 386 (2) ◽  
pp. 95-99 ◽  
Author(s):  
Alexander E.F. Smith ◽  
Farzin Farzaneh ◽  
Kevin G. Ford
Keyword(s):  
Transcription Factors ◽  
Fusion Protein ◽  
Zinc Finger ◽  
Protein Interactions ◽  
Transcriptional Activation ◽  
Zinc Finger Protein ◽  
Zinc Finger Proteins ◽  
Finger Protein ◽  
Finger Extension ◽  
Vp16 Fusion

AbstractIn order to demonstrate that an existing zinc-finger protein can be simply modified to enhance DNA binding and sequence discrimination in both episomal and chromatin contexts using existing zinc-finger DNA recognition code data, and without recourse to phage display and selection strategies, we have examined the consequences of a single zinc-finger extension to a synthetic three-zinc-finger VP16 fusion protein, on transcriptional activation from model target promoters harbouring the zinc-finger binding sequences. We report a nearly 10-fold enhanced transcriptional activation by the four-zinc-finger VP16 fusion protein relative to the progenitor three-finger VP16 protein in transient assays and a greater than five-fold enhancement in stable reporter-gene expression assays. A marked decrease in transcriptional activation was evident for the four-zinc-finger derivative from mutated regulatory regions compared to the progenitor protein, as a result of recognition site-size extension. This discriminatory effect was shown to be protein concentration-dependent. These observations suggest that four-zinc-finger proteins are stable functional motifs that can be a significant improvement over the progenitor three-zinc-finger protein, both in terms of specificity and the ability to target transcriptional function to promoters, and that single zinc-finger extension can therefore have a significant impact on DNA zinc-finger protein interactions. This is a simple route for modifying or enhancing the binding properties of existing synthetic zinc-finger-based transcription factors and may be particularly suited for the modification of endogenous zinc-finger transcription factors for promoter biasing applications.

Cloning and comparative analysis of the bovine, porcine, and equine sex chromosome genes ZFX and ZFY

Genome ◽  
2004 ◽  
Vol 47 (1) ◽  
pp. 74-83 ◽  
Author(s):  
Arkadi Poloumienko
Keyword(s):  
Amino Acids ◽  
Zinc Finger ◽  
Sex Chromosome ◽  
Zinc Finger Proteins ◽  
Mammalian Development ◽  
Coding Regions ◽  
Zinc Finger Motifs ◽  
Internal Exon ◽  
Alternatively Spliced ◽  
Zfy Genes

A growing body of evidence suggests the involvement of sex chromosome genes in mammalian development. We report the cloning and characterization of the complete coding regions of the bovine Y chromosome ZFY and X chromosome ZFX genes, and partial coding regions of porcine and equine ZFX and ZFY genes. Bovine ZFY and ZFX are highly similar to each other and to ZFX and ZFY from other species. While bovine and human ZFY proteins are both 801 amino acids long, bovine ZFX is 5 amino acids shorter than human ZFX. Like in humans, both bovine ZFY and ZFX contain 13 zinc finger motifs and belong to the Krueppel family of C2H2-type zinc finger proteins. The internal exon–intron organization of the bovine, porcine and equine ZFX and ZFY genes has been determined and compared. Within this region, the exon lengths and the positions of the splice sites are conserved, further suggesting a high evolutionary conservation of the ZFX and ZFY genes. Additionally, new alternatively spliced forms of human ZFX have been identified.Key words: sex chromosome genes, zinc finger proteins, ZFX, ZFY, alternative splicing.

scholarly journals C2H2-Type Zinc Finger Proteins (DkZF1/2) Synergistically Control Persimmon Fruit Deastringency

2019 ◽  
Vol 20 (22) ◽  
pp. 5611
Author(s):  
Wajeeha Jamil ◽  
Wei Wu ◽  
Hui Gong ◽  
Jing-Wen Huang ◽  
Mudassar Ahmad ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Zinc Finger ◽  
Protein Interactions ◽  
Zinc Finger Proteins ◽  
Bimolecular Fluorescence Complementation ◽  
Luciferase Assay ◽  
Response Factors ◽  
High Co2 ◽  
Persimmon Fruit ◽  
Genes Encoding

Hypoxic environments are generally undesirable for most plants, but for astringent persimmon, high CO2 treatment (CO2 > 90%), also termed artificial high-CO2 atmosphere (AHCA), causes acetaldehyde accumulation and precipitation of soluble tannins and could remove astringency. The multiple transcriptional regulatory linkages involved in persimmon fruit deastringency have been advanced significantly by characterizing the ethylene response factors (ERFs), WRKY and MYB; however, the involvement of zinc finger proteins for deastringency has not been investigated. In this study, five genes encoding C2H2-type zinc finger proteins were isolated and designed as DkZF1-5. Phylogenetic and sequence analyses suggested the five DkZFs could be clustered into two different subgroups. qPCR analysis indicated that transcript abundances of DkZF1/4 were significantly upregulated during AHCA treatment (1% O2 and 95% CO2) at day 1, DkZF2/5 at both day 1 and 2, while DkZF3 at day 2. Dual-luciferase assay indicated DkZF1 and DkZF2 as the activators of deastringency-related structural genes (DkPDC2 and DkADH1) and transcription factors (DkERF9/10). Moreover, combinative effects between various transcription factors were investigated, indicating that DkZF1 and DkZF2 synergistically showed significantly stronger activations on the DkPDC2 promoter. Further, both bimolecular fluorescence complementation (BiFC) and yeast two hybrid (Y2H) assays confirmed that DkZF2 had protein–protein interactions with DkZF1. Thus, these findings illustrate the regulatory mechanisms of zinc finger proteins for persimmon fruit deastringency under AHCA.

scholarly journals Several One-Domain Zinc Finger µ-Proteins of Haloferax Volcanii Are Important for Stress Adaptation, Biofilm Formation, and Swarming

Genes ◽  
2019 ◽  
Vol 10 (5) ◽  
pp. 361 ◽  
Author(s):  
Chantal Nagel ◽  
Anja Machulla ◽  
Sebastian Zahn ◽  
Jörg Soppa
Keyword(s):  
Zinc Finger ◽  
Biofilm Formation ◽  
Synthetic Medium ◽  
Zinc Finger Proteins ◽  
Haloferax Volcanii ◽  
Deletion Mutants ◽  
Biological Functions ◽  
Loss Of Function ◽  
Wild Type ◽  
Single Exception

Zinc finger domains are highly structured and can mediate interactions to DNA, RNA, proteins, lipids, and small molecules. Accordingly, zinc finger proteins are very versatile and involved in many biological functions. Eukaryotes contain a wealth of zinc finger proteins, but zinc finger proteins have also been found in archaea and bacteria. Large zinc finger proteins have been well studied, however, in stark contrast, single domain zinc finger µ-proteins of less than 70 amino acids have not been studied at all, with one single exception. Therefore, 16 zinc finger µ-proteins of the haloarchaeon Haloferax volcanii were chosen and in frame deletion mutants of the cognate genes were generated. The phenotypes of mutants and wild-type were compared under eight different conditions, which were chosen to represent various pathways and involve many genes. None of the mutants differed from the wild-type under optimal or near-optimal conditions. However, 12 of the 16 mutants exhibited a phenotypic difference under at least one of the four following conditions: Growth in synthetic medium with glycerol, growth in the presence of bile acids, biofilm formation, and swarming. In total, 16 loss of function and 11 gain of function phenotypes were observed. Five mutants indicated counter-regulation of a sessile versus a motile life style in H. volcanii. In conclusion, the generation and analysis of a set of deletion mutants demonstrated the high importance of zinc finger µ-proteins for various biological functions, and it will be the basis for future mechanistic insight.

scholarly journals Systematic Investigation of Scutellariae Barbatae Herba for Treating Hepatocellular Carcinoma Based on Network Pharmacology

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Benjiao Gong ◽  
Yanlei Kao ◽  
Chenglin Zhang ◽  
Fudong Sun ◽  
Huishan Zhao
Keyword(s):  
Hepatocellular Carcinoma ◽  
Systematic Investigation ◽  
Network Pharmacology ◽  
Biological Processes ◽  
Depth Analysis ◽  
Neutrophil Degranulation ◽  
Long Time ◽  
Underlying Mechanisms ◽  
Related Mortality ◽  
Target Fishing

As the fifth most common type of malignant cancers globally, hepatocellular carcinoma (HCC) is the second leading cause of cancer-related mortality worldwide. As a long-time medicinal herb in Traditional Chinese Medicine (TCM), Scutellariae Barbatae Herba (SBH) has also been used for treating various cancers including HCC, but its underlying mechanisms have not been completely clarified. Presently, an innovative network-pharmacology platform was introduced to systematically elucidate the pharmacological mechanisms of SBH against HCC, adopting active ingredients prescreening, target fishing, and network analysis. The results revealed that SBH appeared to work on HCC probably through regulating 4 molecular functions, 20 biological processes, and hitting on 21 candidate targets involved in 40 pathways. By in-depth analysis of the first-ranked signaling pathway and hit genes, only TTR was highly and specially expressed in the liver tissue. TTR might play a crucial role in neutrophil degranulation pathway during SBH against HCC. Hence, TTR might become a therapeutic target of HCC. The study investigated the anti-hepatoma mechanisms of SBH from a holistic perspective, which provided a theoretical foundation for further experimental research and rational clinical application of SBH.

scholarly journals Zinc Finger Proteins as Designer Transcription Factors

2000 ◽  
Vol 275 (12) ◽  
pp. 8742-8748 ◽  
Author(s):  
Jong Seok Kang ◽  
Jin-Soo Kim
Keyword(s):  
Transcription Factors ◽  
Zinc Finger ◽  
Zinc Finger Proteins

scholarly journals KRAB-Zinc Finger Proteins: A Repressor Family Displaying Multiple Biological Functions

2013 ◽  
Vol 14 (4) ◽  
pp. 268-278 ◽  
Author(s):  
Angelo Lupo ◽  
Elena Cesaro ◽  
Giorgia Montano ◽  
Diana Zurlo ◽  
Paola Izzo ◽  
...  
Keyword(s):  
Zinc Finger ◽  
Zinc Finger Proteins ◽  
Biological Functions

scholarly journals Specific Recognition of ZNF217 and Other Zinc Finger Proteins at a Surface Groove of C-Terminal Binding Proteins

2006 ◽  
Vol 26 (21) ◽  
pp. 8159-8172 ◽  
Author(s):  
Kate G. R. Quinlan ◽  
Marco Nardini ◽  
Alexis Verger ◽  
Pierangelo Francescato ◽  
Paul Yaswen ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Transcription Factors ◽  
Zinc Finger ◽  
Target Gene ◽  
Zinc Finger Protein ◽  
Zinc Finger Proteins ◽  
Repressor Protein ◽  
Finger Protein ◽  
Surface Groove ◽  
Binding Cleft

ABSTRACT Numerous transcription factors recruit C-terminal binding protein (CtBP) corepressors. We show that the large zinc finger protein ZNF217 contacts CtBP. ZNF217 is encoded by an oncogene frequently amplified in tumors. ZNF217 contains a typical Pro-X-Asp-Leu-Ser (PXDLS) motif that binds in CtBP's PXDLS-binding cleft. However, ZNF217 also contains a second motif, Arg-Arg-Thr (RRT), that binds a separate surface on CtBP. The crystal structure of CtBP bound to an RRTGAPPAL peptide shows that it contacts a surface crevice distinct from the PXDLS binding cleft. Interestingly, both PXDLS and RRT motifs are also found in other zinc finger proteins, such as RIZ. Finally, we show that ZNF217 represses several promoters, including one from a known CtBP target gene, and mutations preventing ZNF217's contact with CtBP reduce repression. These results identify a new CtBP interaction motif and establish ZNF217 as a transcriptional repressor protein that functions, at least in part, by associating with CtBP.

The Arms Race Between KRAB–Zinc Finger Proteins and Endogenous Retroelements and Its Impact on Mammals

2019 ◽  
Vol 53 (1) ◽  
pp. 393-416 ◽  
Author(s):  
Melania Bruno ◽  
Mohamed Mahgoub ◽  
Todd S. Macfarlan
Keyword(s):  
Transcription Factors ◽  
Structure Function ◽  
Human Genome ◽  
Zinc Finger ◽  
Driving Force ◽  
Zinc Finger Proteins ◽  
Arms Race ◽  
Host Genome ◽  
Current Understanding ◽  
Genome Integrity

Nearly half of the human genome consists of endogenous retroelements (EREs) and their genetic remnants, a small fraction of which carry the potential to propagate in the host genome, posing a threat to genome integrity and cell/organismal survival. The largest family of transcription factors in tetrapods, the Krüppel-associated box domain zinc finger proteins (KRAB-ZFPs), binds to specific EREs and represses their transcription. Since their first appearance over 400 million years ago, KRAB-ZFPs have undergone dramatic expansion and diversification in mammals, correlating with the invasions of new EREs. In this article we review our current understanding of the structure, function, and evolution of KRAB-ZFPs and discuss growing evidence that the arms race between KRAB-ZFPs and the EREs they target is a major driving force for the evolution of new traits in mammals, often accompanied by domestication of EREs themselves.

scholarly journals A Fungal Family of Transcriptional Regulators: the Zinc Cluster Proteins

2006 ◽  
Vol 70 (3) ◽  
pp. 583-604 ◽  
Author(s):  
Sarah MacPherson ◽  
Marc Larochelle ◽  
Bernard Turcotte
Keyword(s):  
Zinc Finger ◽  
Fungal Pathogens ◽  
Budding Yeast ◽  
Transcriptional Regulators ◽  
Zinc Finger Proteins ◽  
Pleiotropic Drug Resistance ◽  
Binding Motifs ◽  
Zinc Cluster ◽  
Primary And Secondary Metabolism ◽  
Wide Range

SUMMARY The trace element zinc is required for proper functioning of a large number of proteins, including various enzymes. However, most zinc-containing proteins are transcription factors capable of binding DNA and are named zinc finger proteins. They form one of the largest families of transcriptional regulators and are categorized into various classes according to zinc-binding motifs. This review focuses on one class of zinc finger proteins called zinc cluster (or binuclear) proteins. Members of this family are exclusively fungal and possess the well-conserved motif CysX2CysX6CysX5-12CysX2CysX6-8Cys. The cysteine residues bind to two zinc atoms, which coordinate folding of the domain involved in DNA recognition. The first- and best-studied zinc cluster protein is Gal4p, a transcriptional activator of genes involved in the catabolism of galactose in the budding yeast Saccharomyces cerevisiae. Since the discovery of Gal4p, many other zinc cluster proteins have been characterized; they function in a wide range of processes, including primary and secondary metabolism and meiosis. Other roles include regulation of genes involved in the stress response as well as pleiotropic drug resistance, as demonstrated in budding yeast and in human fungal pathogens. With the number of characterized zinc cluster proteins growing rapidly, it is becoming more and more apparent that they are important regulators of fungal physiology.

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