Recognition Code of ZNF191(243-368) and Its Interaction with DNA

Zhao, Dongxin; Huang, Zhong‐Xian

doi:10.1155/2015/416751

Cited by 6 publications

(4 citation statements)

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“…C2H2 Znf's are the most common DNA-binding motifs found in eukaryotic transcription factors and have also been identi ed in prokaryotes. 19,52 Transcription factors usually contain several Znf's (each with a conserved beta/beta/alpha structure) capable of making multiple contacts along with the DNA, where the C2H2 Znf motifs recognize DNA sequences by binding to the major groove of DNA via a short alpha-helix in the Znf, the Znf spanning 3-4 bases of the DNA. 20 C2H2 Znf's can also bind to RNA and protein targets.…”

Section: Molecular Genetics and Neurobiological Effectsmentioning

confidence: 99%

“…1,[12][13][14][15][16] The APTX gene encodes for a protein called Aprataxin, composed of three domains that share distant homology with the amino-terminal domain of polynucleotide kinase 3′-phosphatase (PNKP), with histidine-triad (HIT) proteins and with DNA-binding C2H2 zinc-nger proteins. 14,15,[17][18][19][20][21][22] Given the role of PNKP in DNA single-strand break reparation, Aprataxin has been involved in the repair of DNA in cells of various tissues, including the brain, spinal cord, and muscles. 15,[23][24][25][26] The APTX gene is widely expressed in the nervous system and detected in the cerebellum, basal ganglia, cerebral cortex, and spinal cord.…”

Section: Introductionmentioning

confidence: 99%

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Ataxia with Ocular Apraxia Type 1 (AOA1) (APTX, W279* Mutation): Neurological, Neuropsychological, and Molecular Outlining of a Heterogenous Phenotype in Four Colombian Siblings

et al. 2022

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Hereditary ataxias are a group of devastating neurological disorders that affect coordination of gait and are often associated with poor coordination of hands, speech, and eye movements. Ataxia with Ocular Apraxia type 1 (AOA1) (OMIM: 606350.0006) is characterized by slowly progressive symptoms of childhood-onset and pathogenic mutations in APTX; the only known cause underpinning AOA1. APTX encodes the protein Aprataxin, composed of three domains sharing homology with proteins involved in DNA damage, signaling, and repair. We present four siblings from an endogamic family in a rural, isolated town of Colombia with ataxia and ocular apraxia of childhood-onset and con rmed molecular diagnosis of AOA1, homozygous for the W279* p.Trp279Ter mutation. We predicted the mutated APTX with Alpha Fold to demonstrate the effects of this stop-gain mutation that deletes three beta helices encoded by amino acid 270 to 339 rescinding the C2H2-type zinc ngers (Znf) (C2H2 Znf) DNA-binding and DNArepair domain and the whole tridimensional structure of the APTX. All siblings exhibited different ages of onset (4, 6, 8, and 11 y/o) and heterogeneous patterns of dysarthria (ranging from absence to mildmoderate dysarthria). Neuropsychological evaluation showed no neurocognitive impairment in three siblings, but one sibling showed temporospatial disorientation, semantic and phonologic uency impairment, episodic memory affection, constructional apraxia, moderate anomia, low executive function, and symptoms of depression. This heterogeneous phenotype suggests genetic interactions can shape the natural history of AOA1. To our knowledge, this report represents the most extensive series of siblings affected with AOA1 in Latin America, and the genetic analysis completed adds important knowledge to outline this family's disease and general complex phenotype of hereditary ataxias.

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Section: Molecular Genetics and Neurobiological Effectsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Ataxia with Ocular Apraxia Type 1 (AOA1) (APTX, W279* Mutation): Neurological, Neuropsychological, and Molecular Outlining of a Heterogenous Phenotype in Four Colombian Siblings

et al. 2022

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“…Here, we chose plasmid pGEX-B containing a GGAGGG site to study the hydrolytic activity of His-tagged proteins. The pGEX-B plasmid was obtained from the DNA binding experiment of ZNF191(243-368) [ 27 ], and the electrophoresis results were shown in Figure 6 . The plasmids all had two main bands.…”

Section: Resultsmentioning

confidence: 99%

Effect of His-Tag on Expression, Purification, and Structure of Zinc Finger Protein, ZNF191(243-368)

Zhao

Huang

2016

Bioinorganic Chemistry and Applications

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Zinc finger proteins are associated with hereditary diseases and cancers. To obtain an adequate amount of zinc finger proteins for studying their properties, structure, and functions, many protein expression systems are used. ZNF191(243-368) is a zinc finger protein and can be fused with His-tag to generate fusion proteins such as His6-ZNF191(243-368) and ZNF191(243-368)-His8. The purification of His-tag protein using Ni-NTA resin can overcome the difficulty of ZNF191(243-368) separation caused by inclusion body formation. The influences of His-tag on ZNF191(243-368) properties and structure were investigated using spectrographic techniques and hydrolase experiment. Our findings suggest that insertion of a His-tag at the N-terminal or C-terminal end of ZNF191(243-368) has different effects on the protein. Therefore, an expression system should be considered based on the properties and structure of the protein. Furthermore, the hydrolase activity of ZNF191(243-368)-His8 has provided new insights into the design of biological functional molecules.

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“…Many of the C2H2-type ZNFs are conserved throughout evolution, playing vital roles in embryo development and tissue differentiation 8. Zinc finger protein 24 (ZNF24) belongs to the C2H2-type subfamily and can also function as a DNA-binding transcription factor 9,10. ZNF24 was initially termed ZNF KOX17 by Rousseau-Merck et al11 in 1991, which was mapped to 18q12 by somatic cell hybrid analysis and in situ chromosomal hybridization.…”

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confidence: 99%

Zinc Finger Protein 24 is a Prognostic Factor in Ovarian Serous Carcinoma

Chen

Guo

Yuan³

et al. 2021

Applied Immunohistochemistry &Amp; Molecular Morphology

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Objective: As a member of the zinc finger protein family, zinc finger protein 24 (ZNF24) contains a Cys2His2 zinc finger domain and acts as a transcription factor. ZNF24 has been reported to be downregulated in gastric cancer and breast cancer. However, little is known about its expression and function in ovarian serous carcinoma (OSC).Patients and Methods: We collected 117 OSC patients during 2011 to 2017 and retrospectively retrieved their clinicopathologic characteristics as well as their survival data. Protein level was analyzed by immunohistochemistry, mRNA level was evaluated by RT-qPCR assay, and transcriptional data was obtained from TCGA data sets. The correlations between ZNF24 expression and patients' features were assessed using χ 2 test. Univariate and multivariate analyses were used to identify the prognosis predicative potential of ZNF24 in OSC. The function of ZNF24 in the epithelial ovarian cancer cells was also verified by in vitro cellular experiments.Results: Among the 117 cases, ZNF24 was downregulated in 52 OSC samples (44.6%) and significantly correlated with tumor stages. According to univariate and multivariate analyses, ZNF24 can act as an independent prognostic indicator for the overall survival of OSC patients, whose lower expression was associated with poorer clinical outcomes. Ectopic overexpression and knockdown assays indicated that ZNF24 can negatively regulate the OSC cell viability.Conclusions: OSC patients with low level of ZNF24 have worse overall survival compared with those possess high-ZNF24 expression. Downregulated ZNF24 may be involved in the proliferation of OSC, and ZNF24 expression can serve as an independent survival predictor.

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Recognition Code of ZNF191(243-368) and Its Interaction with DNA

Cited by 6 publications

References 44 publications

Ataxia with Ocular Apraxia Type 1 (AOA1) (APTX, W279* Mutation): Neurological, Neuropsychological, and Molecular Outlining of a Heterogenous Phenotype in Four Colombian Siblings

Ataxia with Ocular Apraxia Type 1 (AOA1) (APTX, W279* Mutation): Neurological, Neuropsychological, and Molecular Outlining of a Heterogenous Phenotype in Four Colombian Siblings

Effect of His-Tag on Expression, Purification, and Structure of Zinc Finger Protein, ZNF191(243-368)

Zinc Finger Protein 24 is a Prognostic Factor in Ovarian Serous Carcinoma

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