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DNA-binding proteins

Hua Zhu, Yue Huang, Heling Su, Yili Ma, Yiming Tao, D Joshua Liao, Yongming Liu, Zhenbo Feng
Since the early 1990s, multiple human estrogen receptor-α (hER-α) splice variants have been identified, of which the majority contain ≥1 deleted exon, and some are expressed as proteins with modified functions from the wild-type 66 kDa hER-α (ER-α66). In the present study, a novel hER-α splice variant, ER-α30, was identified and cloned from clinical breast cancer tissue. The ER-α30 sequence lacked a ligand-binding domain and a ligand-dependent transcriptional activation domain but retained the N-terminal transcriptional activation domain, the DNA-binding domain and a partial hinge domain, and possesses a unique 10-amino-acid domain...
April 2018: Oncology Letters
Pei-Hua Li, Lin Wang, Yao-Jie Pan, Miao-Miao Sang, Jun-Nian Zheng, Dong-Sheng Pei
c-Jun activation domain-binding protein-1 (Jab1) is a multifunctional protein involved in cell proliferation and apoptosis, DNA damage and repair and genome stability. In a number of types of human carcinoma, the abnormal expression of Jab1 is associated with poor prognosis, suggesting that Jab1 serves a vital function in tumorigenesis. However, the functional effects and the underlying molecular mechanisms of Jab1 in laryngeal squamous cell carcinoma (LSCC) progression remain poorly understood. The results of the present study demonstrate that downregulating Jab1 expression promotes LSCC apoptosis while inhibiting the proliferation of LSCC cells...
April 2018: Oncology Letters
Anamika Patel, Peng Yang, Matthew Tinkham, Mihika Pradhan, Ming-An Sun, Yixuan Wang, Don Hoang, Gernot Wolf, John R Horton, Xing Zhang, Todd Macfarlan, Xiaodong Cheng
Tandem zinc finger (ZF) proteins are the largest and most rapidly diverging family of DNA-binding transcription regulators in mammals. ZFP568 represses a transcript of placental-specific insulin like growth factor 2 (Igf2-P0) in mice. ZFP568 binds a 24-base pair sequence-specific element upstream of Igf2-P0 via the eleven-ZF array. Both DNA and protein conformations deviate from the conventional one finger-three bases recognition, with individual ZFs contacting 2, 3, or 4 bases and recognizing thymine on the opposite strand...
March 13, 2018: Cell
Kentaro Hosokawa, Fumio Arai
In order to maintain the homeostasis of the hematopoietic system, hematopoietic stem cells (HSCs) need to be maintained while slowly dividing over their lifetime. However, repeated cell divisions lead to the gradual accumulation of DNA damage and ultimately impair HSC function. Since telomeres are particularly fragile when subjected to replication stress, cells have several defense machinery to protect telomeres. Moreover, HSCs must protect their genome against possible DNA damage, while maintaining telomere length...
March 17, 2018: International Journal of Hematology
Seaim Lwin Aye, Kei Fujiwara, Asuka Ueki, Nobuhide Doi
Although compartmentalized self-replication (CSR) and compartmentalized partnered replication (CPR) are powerful tools for directed evolution of proteins and gene circuits, limitations remain in the emulsion PCR process with the wild-type Taq DNA polymerase used so far, including long run times, low amounts of product, and false negative results due to inhibitors. In this study, we developed a high-efficiency mutant of DNA polymerase I from Thermus thermophilus HB27 (Tth pol) suited for CSR and CPR. We modified the wild-type Tth pol by (i) deletion of the N-terminal 5' to 3' exonuclease domain, (ii) fusion with the DNA-binding protein Sso7d, (iii) introduction of four known effective point mutations from other DNA polymerase mutants, and (iv) codon optimization to reduce the GC content...
March 14, 2018: Biochemical and Biophysical Research Communications
Bita Zamiri, Mila Mirceta, Rashid Abu-Ghazalah, Marc S Wold, Christopher E Pearson, Robert B Macgregor
BACKGROUND: Expansion of the C9orf72 hexanucleotide repeat (GGGGCC)n •(GGCCCC)n is the most common cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Both strands of the C9orf72 repeat have been shown to form unusual DNA and RNA structures that are thought to be involved in mutagenesis and/or pathogenesis. We previously showed that the C-rich DNA strands from the C9orf72 repeat can form four-stranded quadruplexes at neutral pH. The cytosine residues become protonated under slightly acidic pH (pH 4...
March 14, 2018: Biochimica et Biophysica Acta
Deepti Singh, Shwetha Narayanamoorthy, Sunita Gamre, Ananda Guha Majumdar, Manish Goswami, Umesh Gami, Susan Cherian, Mahesh Subramanian
Antibiotic resistance is a global problem and there is an urgent need to augment the arsenal against pathogenic bacteria. The emergence of different drug resistant bacteria is threatening human lives to be pushed towards the pre-antibiotic era. Botanical sources remain a vital source of diverse organic molecules that possess antibacterial property as well as augment existing antibacterial molecules. Piper betle, a climber, is widely used in south and south-east Asia whose leaves and nuts are consumed regularly...
March 14, 2018: Free Radical Biology & Medicine
Ibtehaj Naqvi, Ruwan Gunaratne, Jessica E McDade, Angelo Moreno, Rachel E Rempel, Douglas C Rouse, Silvia Gabriela Herrera, David S Pisetsky, Jaewoo Lee, Rebekah R White, Bruce A Sullenger
Nucleic acid binding polymers (NABPs) have been extensively used as vehicles for DNA and RNA delivery. More recently, we discovered that a subset of these NABPs can also serve as anti-inflammatory agents by capturing pro-inflammatory extracellular nucleic acids and associated protein complexes that promote activation of toll-like receptors (TLRs) in diseases such as lupus erythematosus. Nucleic-acid-mediated TLR signaling also facilitates tumor progression and metastasis in several cancers, including pancreatic cancer (PC)...
February 23, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
Shintaro Yamada, Kazuto Kugou, Da-Qiao Ding, Yurika Fujita, Yasushi Hiraoka, Hiroshi Murakami, Kunihiro Ohta, Takatomi Yamada
Meiotic recombination ensures faithful chromosome segregation and confers genetic diversity to gametes, and thus, is a key DNA-templated reaction not only for sexual reproduction, but also evolution. This recombination is initiated by programmed DNA double strand breaks (DSBs), which are mainly formed at recombination hotspots. As meiotic DSB formation requires multiple proteins, it is regulated by chromatin structure. In particular, DSB occurs in a higher-order chromatin architecture termed "axis-loop", in which many loops protrude from proteinaceous axis...
March 16, 2018: Current Genetics
Yuan Gao, Xiaoju Li, Zhen Shu, Kuo Zhang, Xiaochang Xue, Weina Li, Qiang Hao, Zhaowei Wang, Wangqian Zhang, Shuning Wang, Cheng Zeng, Dong Fan, Wei Zhang, Yingqi Zhang, Huadong Zhao, Meng Li, Cun Zhang
FOXP3 is an important X-linked suppressor of breast cancer. It is reported that FOXP3 is usually mutant, absent, or cytoplasmic distribution in breast cancer cells, which increases the risk of breast cancer. However, in our study the full-length FOXP3 transcript can be detected in breast cancer cells and nuclear FOXP3 is expressed in some breast cancer samples. Therefore, an important question is how the tumor-suppressive function of wild-type FOXP3 is negated in these cancers. We found that Gal-1 is a novel interacting protein of FOXP3 in breast cancer...
March 16, 2018: Cell Death & Disease
Zhaojian Xiang, Weike Li, Lixue Wang, Jicai Yi, Kaiwen Chen, Mei Hong
Organic anion-transporting polypeptides (OATPs; gene symbol SLCO) are membrane transporters that mediate the transport of wide ranges of compounds. Expression of different OATP members has been reported in the kidney, liver, placenta, brain, and intestine. Due to their broad substrate spectra and wide distribution within human body, these transporters have been proposed to play key roles in the influx transport of many oral drugs. Inflammation is known to regulate the expression and functions of many drug-metabolizing enzymes and drug transporters...
March 16, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
Aykut Erbaş, Monica Olvera de la Cruz, John F Marko
We study unbinding of multivalent cationic ligands from oppositely charged polymeric binding sites sparsely grafted on a flat neutral substrate. Our molecular dynamics simulations are suggested by single-molecule studies of protein-DNA interactions. We consider univalent salt concentrations spanning roughly a 1000-fold range, together with various concentrations of excess ligands in solution. To reveal the ionic effects on unbinding kinetics of spontaneous and facilitated dissociation mechanisms, we treat electrostatic interactions both at a Debye-Hückel (DH) (or implicit ions, i...
February 2018: Physical Review. E
Min Young Kim, Ji Sook Kim, Seung Han Son, Chang Su Lim, Hea Young Eum, Dae Hyun Ha, Mi Ae Park, Eun Jung Baek, Buom-Yong Ryu, Ho Chul Kang, Vladimir N Uversky, Chul Geun Kim
During hematopoiesis, red blood cells originate from the hematopoietic stem cell reservoir. Although the regulation of erythropoiesis and globin expression has been intensively investigated, the underlining mechanisms are not fully understood, including the interplay between transcription factors and epigenetic factors. Here, we uncover that the Mbd2-free NuRD chromatin remodeling complex potentiates erythroid differentiation of proerythroblasts via managing functions of the CP2c complexes. We found that both Mbd2 and Mbd3 expression is downregulated during differentiation of MEL cells in vitro and in normal erythropoiesis in mouse bone marrow, and Mbd2 downregulation is crucial for erythropoiesis...
March 14, 2018: Nucleic Acids Research
Neha J Pancholi, Matthew D Weitzman
During viral replication in the nucleus, the DNA genomes of adenoviruses are accessible to cellular DNA-binding proteins. Human adenovirus type 5 (Ad5) targets the cellular Mre11-Rad50-Nbs1 complex (MRN) to evade detection by the DNA damage response (DDR). Ad5 mutants that cannot target MRN have reduced viral propagation. Previous studies showed that diverse adenovirus serotypes interact differently with MRN. While these studies revealed diverse MRN interactions among serotypes, it remains unclear how these differences influence viral replication...
March 13, 2018: Virology
Camilla Björkegren, Laura Baranello
Although our knowledge of chromatin organization has advanced significantly in recent years, much about the relationships between different features of genome architecture is still unknown. Folding of mammalian genomes into spatial domains is thought to depend on architectural proteins, other DNA-binding proteins, and different forms of RNA. In addition, emerging evidence points towards the possibility that the three-dimensional organisation of the genome is controlled by DNA topology. In this scenario, cohesin, CCCTC-binding factor (CTCF), transcription, DNA supercoiling, and topoisomerases are integrated to dictate different layers of genome organization, and the contribution of all four to gene control is an important direction of future studies...
March 16, 2018: International Journal of Molecular Sciences
Evgenia N Nikolova, Robyn L Stanfield, Jane Dyson, Peter E Wright
Many eukaryotic transcription factors recognize the epigenetic marker 5-methylcytosine (mC) at CpG sites in DNA. Despite their structural diversity, methyl-CpG-binding proteins (MBPs) share a common mode of recognition of mC methyl groups that involves hydrophobic pockets and weak hydrogen bonds of the CH---O type. The zinc finger protein Kaiso possesses a remarkably high specificity for methylated over unmethylated CpG sites. A key contribution to this specificity is provided by glutamate 535 (E535), which is optimally positioned to form multiple interactions with mCpG, including direct CH---O hydrogen bonds...
March 16, 2018: Biochemistry
Fırat Kurt, Ertugrul Filiz
Iron (Fe) is an essential element for plant life. Its deficiency impedes growth and development and excessive iron can cause the toxic effect via the Fenton reaction. Thus, plants have developed various mechanisms to acquire, distribute and utilize Fe for the maintenance of their iron homeostasis at cellular and systemic levels. A basic helix-loop-helix (bHLH) transcription factor family plays essential roles in many regulatory and development processes in plants. In this study, we aimed to understand the roles of bHLH38, bHLH39, bHLH100 and bHLH101 genes for Fe homeostasis in Arabidopsis, tomato, rice, soybean and maize species by using bioinformatics approaches...
March 15, 2018: Biometals: An International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine
Daniela Cecconi, Luca Dalle Carbonare, Antonio Mori, Samuele Cheri, Michela Deiana, Jessica Brandi, Vincenzo Degaetano, Valentina Masiero, Giulio Innamorati, Monica Mottes, Giovanni Malerba, Maria Teresa Valenti
Melanoma is an aggressive skin cancer; an early detection of the primary tumor may improve its prognosis. Despite many genes have been shown to be involved in melanoma, the full framework of melanoma transformation has not been completely explored. The characterization of pathways involved in tumor restraint in in vitro models may help to identify oncotarget genes. We therefore aimed to probe novel oncotargets through an integrated approach involving proteomic, gene expression and bioinformatic analysis We investigated molecular modulations in melanoma cells treated with ascorbic acid, which is known to inhibit cancer growth at high concentrations...
February 20, 2018: Oncotarget
Satoshi Suzuki, Moriya Iwaizumi, Hidetaka Yamada, Tomohiro Sugiyama, Yasushi Hamaya, Takahisa Furuta, Shigeru Kanaoka, Haruhiko Sugimura, Hiroaki Miyajima, Satoshi Osawa, John M Carethers, Ken Sugimoto
Backgrounds: Trifluridine is an active antitumor component of TAS-102 that resembles 5-fluorouracil. Although patients with advanced colorectal cancer (CRC) exhibiting a mismatch repair (MMR) deficiency reportedly do not benefit from 5-fluorouracil-based chemotherapy and we previously reported that truncated methyl-CpG binding domain protein 4 (MBD4) enhances 5-fluorouracil cytotoxicity in MMR-deficient CRC cells, little is known regarding the effect of MMR deficiency on trifluridine cytotoxicity in CRC...
February 20, 2018: Oncotarget
Jing Zhu, Ying Xin, Xiaoliang Liu, Ying Wang, Ying Liu
Non-small cell lung cancer (NSCLC) accounts for ~85% of lung cancer cases worldwide. Current guidelines recommend the use of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors for patients with NSCLC. The EGF/EGFR signaling pathway has been demonstrated to activate nuclear factor (NF)-κB, which may inhibit tumor necrosis factor (TNF)-α induced cell apoptosis. The aim of the present study was to investigate whether inhibiting the EGF/EGFR signaling pathway sensitizes NSCLC cell lines to TNF-α-induced apoptosis...
April 2018: Experimental and Therapeutic Medicine
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