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https://www.readbyqxmd.com/read/28318631/the-antihelmenthic-phosphate-niclosamide-impedes-renal-fibrosis-by-inhibiting-homeodomain-interacting-protein-kinase-2-expression
#1
Xiaoyan Chang, Xin Zhen, Jixing Liu, Xiaomei Ren, Zheng Hu, Zhanmei Zhou, Fengxin Zhu, Ke Ding, Jing Nie
Renal fibrosis is the final common pathway of all varieties of progressive chronic kidney disease. However, there are no effective therapies to prevent or slow the progression of renal fibrosis. Niclosamide is a US Food and Drug Administration-approved oral antihelminthic drug used for treating most tapeworm infections. Here, we demonstrated that phosphate niclosamide, the water-soluble form of niclosamide, significantly reduced proteinuria, glomerulosclrotic lesions, and interstitial fibrosis in a murine model of adriamycin nephropathy...
March 16, 2017: Kidney International
https://www.readbyqxmd.com/read/28302169/two-novel-lhx3-mutations-in-patients-with-combined-pituitary-hormone-deficiency-including-cervical-rigidity-and-sensorineural-hearing-loss
#2
Khushnooda Ramzan, Bassam Bin-Abbas, Lolwa Al-Jomaa, Rabab Allam, Mohammed Al-Owain, Faiqa Imtiaz
BACKGROUND: Congenital combined pituitary hormone deficiency (CPHD) is a rare heterogeneous group of conditions. CPHD-type 3 (CPHD3; MIM# 221750) is caused by recessive mutations in LHX3, a LIM-homeodomain transcription factor gene. The isoforms of LHX3 are critical for pituitary gland formation and specification of the anterior pituitary hormone-secreting cell types. They also play distinct roles in the development of neuroendocrine and auditory systems. CASE PRESENTATION: Here, we summarize the clinical, endocrinological, radiological and molecular features of three patients from two unrelated families...
March 16, 2017: BMC Endocrine Disorders
https://www.readbyqxmd.com/read/28296185/chip-ldb1-interacts-with-tailup-islet1-to-regulate-cardiac-gene-expression-in-drosophila
#3
Kathrin Werner, Cornelia Donow, Petra Pandur
The LIM-homeodomain transcription factor Tailup (Tup) is a component of the complex cardiac transcriptional network governing specification and differentiation of cardiac cells in Drosophila. LIM-domain containing factors are known to interact with the adaptor molecule Chip/Ldb1 to form higher order protein complexes to regulate gene expression thereby determining a cell's developmental fate. However, with respect to Drosophila heart development, it has not been investigated yet, whether Chip and tup interact to regulate the generation of different cardiac cell types...
March 15, 2017: Genesis: the Journal of Genetics and Development
https://www.readbyqxmd.com/read/28289210/phosphorylation-induced-conformational-dynamics-in-an-intrinsically-disordered-protein-and-potential-role-in-phenotypic-heterogeneity
#4
Prakash Kulkarni, Mohit Kumar Jolly, Dongya Jia, Steven M Mooney, Ajay Bhargava, Luciane T Kagohara, Yihong Chen, Pengyu Hao, Yanan He, Robert W Veltri, Alexander Grishaev, Keith Weninger, Herbert Levine, John Orban
Intrinsically disordered proteins (IDPs) that lack a unique 3D structure and comprise a large fraction of the human proteome play important roles in numerous cellular functions. Prostate-Associated Gene 4 (PAGE4) is an IDP that acts as a potentiator of the Activator Protein-1 (AP-1) transcription factor. Homeodomain-Interacting Protein Kinase 1 (HIPK1) phosphorylates PAGE4 at S9 and T51, but only T51 is critical for its activity. Here, we identify a second kinase, CDC-Like Kinase 2 (CLK2), which acts on PAGE4 and hyperphosphorylates it at multiple S/T residues, including S9 and T51...
March 13, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28286003/recognition-of-histone-h3k14-acylation-by-morf
#5
Brianna J Klein, Johayra Simithy, Xiaolu Wang, JaeWoo Ahn, Forest H Andrews, Yi Zhang, Jacques Côté, Xiaobing Shi, Benjamin A Garcia, Tatiana G Kutateladze
The monocytic leukemia zinc-finger protein-related factor (MORF) is a transcriptional coactivator and a catalytic subunit of the lysine acetyltransferase complex implicated in cancer and developmental diseases. We have previously shown that the double plant homeodomain finger (DPF) of MORF is capable of binding to acetylated histone H3. Here we demonstrate that the DPF of MORF recognizes many newly identified acylation marks. The mass spectrometry study provides comprehensive analysis of H3K14 acylation states in vitro and in vivo...
March 9, 2017: Structure
https://www.readbyqxmd.com/read/28266561/nkx2-1-regulates-the-generation-of-telencephalic-astrocytes-during-embryonic-development
#6
Shilpi Minocha, Delphine Valloton, Yvan Arsenijevic, Jean-René Cardinaux, Raffaella Guidi, Jean-Pierre Hornung, Cécile Lebrand
The homeodomain transcription factor Nkx2.1 (NK2 homeobox 1) controls cell differentiation of telencephalic GABAergic interneurons and oligodendrocytes. Here we show that Nkx2.1 also regulates astrogliogenesis of the telencephalon from embryonic day (E) 14.5 to E16.5. Moreover we identify the different mechanisms by which Nkx2.1 controls the telencephalic astrogliogenesis. In Nkx2.1 knockout (Nkx2.1(-/-)) mice a drastic loss of astrocytes is observed that is not related to cell death. Further, in vivo analysis using BrdU incorporation reveals that Nkx2...
March 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28253300/the-pax-gene-family-highlights-from-cephalopods
#7
Sandra Navet, Auxane Buresi, Sébastien Baratte, Aude Andouche, Laure Bonnaud-Ponticelli, Yann Bassaglia
Pax genes play important roles in Metazoan development. Their evolution has been extensively studied but Lophotrochozoa are usually omitted. We addressed the question of Pax paralog diversity in Lophotrochozoa by a thorough review of available databases. The existence of six Pax families (Pax1/9, Pax2/5/8, Pax3/7, Pax4/6, Paxβ, PoxNeuro) was confirmed and the lophotrochozoan Paxβ subfamily was further characterized. Contrary to the pattern reported in chordates, the Pax2/5/8 family is devoid of homeodomain in Lophotrochozoa...
2017: PloS One
https://www.readbyqxmd.com/read/28251315/genome-wide-analysis-of-the-hd-zip-iv-transcription-factor-family-in-gossypium-arboreum-and-gahdg11-involved-in-osmotic-tolerance-in-transgenic-arabidopsis
#8
Eryong Chen, Xueyan Zhang, Zhaoen Yang, Xiaoqian Wang, Zuoren Yang, Chaojun Zhang, Zhixia Wu, Depei Kong, Zhao Liu, Ge Zhao, Hamama Islam Butt, Xianlong Zhang, Fuguang Li
HD-ZIP IV proteins belong to the homeodomain-leucine zipper (HD-ZIP) transcription factor family and are involved in trichome development and drought stress in plants. Although some functions of the HD-ZIP IV group are well understood in Arabidopsis, little is known about their function in cotton. In this study, HD-ZIP genes were identified from three Gossypium species (G. arboreum, G. raimondii and G. hirsutum) and clustered into four families (HD-ZIP I, II, III and IV) to separate HD-ZIP IV from the other three families...
March 1, 2017: Molecular Genetics and Genomics: MGG
https://www.readbyqxmd.com/read/28249019/genome-wide-characterization-and-expression-profiling-of-hd-zip-gene-family-related-to-abiotic-stress-in-cassava
#9
Zehong Ding, Lili Fu, Yan Yan, Weiwei Tie, Zhiqiang Xia, Wenquan Wang, Ming Peng, Wei Hu, Jiaming Zhang
Homeodomain-leucine zipper (HD-Zip) gene family plays important roles in various abiotic stresses and hormone signaling in plants. However, no information is currently available regarding this family in cassava (Manihot esculenta), an important drought-tolerant crop in tropical and sub-tropical areas. Here, 57 HD-Zip genes (MeHDZ01-57) were identified in the cassava genome, and they were classified into four subfamilies based on phylogenetic analysis, which was further supported by their gene structure and conserved motif characteristics...
2017: PloS One
https://www.readbyqxmd.com/read/28247551/characterization-of-chromosomal-abnormalities-in-pregnancy-losses-reveals-critical-genes-and-loci-for-human-early-development
#10
Yiyun Chen, Justin Bartanus, Desheng Liang, Hongmin Zhu, Amy M Breman, Janice L Smith, Hua Wang, Zhilin Ren, Ankita Patel, Pawel Stankiewicz, David S Cram, Sau Wai Cheung, Lingqian Wu, Fuli Yu
Detailed characterization of chromosomal abnormalities, a common cause for congenital abnormalities and pregnancy loss, is critical for elucidating genes for human fetal development. Here, 2186 product of conception (POC) samples were tested for copy number variations (CNVs) at two clinical diagnostic centers using whole genome sequencing and high-resolution chromosomal microarray analysis. We developed a new gene discovery approach to predict potential developmental genes and identified 275 candidate genes from CNVs detected from both datasets...
February 28, 2017: Human Mutation
https://www.readbyqxmd.com/read/28241740/hinokitiol-induces-dna-demethylation-via-dnmt1-and-uhrf1-inhibition-in-colon-cancer-cells
#11
Jung Seon Seo, Young Ha Choi, Ji Wook Moon, Hyeon Soo Kim, Sun-Hwa Park
BACKGROUND: DNA hypermethylation is a key epigenetic mechanism for the silencing of many genes in cancer. Hinokitiol, a tropolone-related natural compound, is known to induce apoptosis and cell cycle arrest and has anti-inflammatory and anti-tumor activities. However, the relationship between hinokitiol and DNA methylation is not clear. The aim of our study was to explore whether hinokitiol has an inhibitory ability on the DNA methylation in colon cancer cells. RESULTS: MTT data showed that hinokitiol had higher sensitivity in colon cancer cells, HCT-116 and SW480, than in normal colon cells, CCD18Co...
February 27, 2017: BMC Cell Biology
https://www.readbyqxmd.com/read/28236976/homeodomain-interacting-protein-kinases-diverse-and-complex-roles-in-development-and-disease
#12
Jessica A Blaquiere, Esther M Verheyen
The Homeodomain-interacting protein kinase (Hipk) family of proteins plays diverse, and at times conflicting, biological roles in normal development and disease. In this review we will highlight developmental and cellular roles for Hipk proteins, with an emphasis on the pleiotropic and essential physiological roles revealed through genetic studies. We discuss the myriad ways of regulating Hipk protein function, and how these may contribute to the diverse cellular roles. Furthermore we will describe the context-specific activities of Hipk family members in diseases such as cancer and fibrosis, including seemingly contradictory tumor-suppressive and oncogenic activities...
2017: Current Topics in Developmental Biology
https://www.readbyqxmd.com/read/28220140/nbs-lrr-protein-pik-h4-interacts-with-osbihd1-to-balance-rice-blast-resistance-and-growth-by-coordinating-ethylene-brassinosteroid-pathway
#13
Hao Liu, Shuangyu Dong, Fengwei Gu, Wei Liu, Guili Yang, Ming Huang, Wuming Xiao, Yongzhu Liu, Tao Guo, Hui Wang, Zhiqiang Chen, Jiafeng Wang
The regulation of innate immunity and plant growth, along with the trade-off between them, affects the defense and recovery mechanisms of the plant after it is attacked by pathogens. Although it is known that hormonal crosstalk plays a major role in regulating interaction of plant growth and PAMP-triggered immunity, the relationship between plant growth and effector-triggered immunity (ETI) remains unclear. In a large-scale yeast two-hybrid screening for Pik-H4-interacting proteins, a homeodomain transcription factor OsBIHD1 was identified, which is previously known to function in biotic and abiotic stress responses...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28220029/a-novel-inhibitor-of-homeodomain-interacting-protein-kinase-2-mitigates-kidney-fibrosis-through-inhibition-of-the-tgf-%C3%AE-1-smad3-pathway
#14
Ruijie Liu, Bhaskar Das, Wenzhen Xiao, Zhengzhe Li, Huilin Li, Kyung Lee, John Cijiang He
Homeodomain interacting protein kinase 2 (HIPK2) is a critical regulator of multiple profibrotic pathways, including that of TGF-β1/Smad3. Genetic ablation of HIPK2 was shown previously to significantly reduce renal fibrosis in the experimental unilateral ureteral obstruction model and Tg26 mice, a model of HIV-associated nephropathy. To develop specific pharmacologic inhibitors of HIPK2 for antifibrotic therapy, we designed and synthesized small molecule inhibitor compounds on the basis of the predicted structure of HIPK2...
February 20, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28215221/targeting-chromatin-remodeling-in-inflammation-and-fibrosis
#15
J Yang, B Tian, A R Brasier
Mucosal surfaces of the human body are lined by a contiguous epithelial cell surface that forms a barrier to aerosolized pathogens. Specialized pattern recognition receptors detect the presence of viral pathogens and initiate protective host responses by triggering activation of the nuclear factor κB (NFκB)/RelA transcription factor and formation of a complex with the positive transcription elongation factor (P-TEFb)/cyclin-dependent kinase (CDK)9 and Bromodomain-containing protein 4 (BRD4) epigenetic reader...
2017: Advances in Protein Chemistry and Structural Biology
https://www.readbyqxmd.com/read/28213137/foxo1-is-a-downstream-effector-of-isl1-in-direct-pathway-striatal-projection-neuron-development-within-the-embryonic-mouse-telencephalon
#16
R R Waclaw, L A Ehrman, P Merchan-Sala, V Kohli, D Nardini, K Campbell
Recent studies have shown that the LIM-homeodomain transcription factor Isl1 is required for the survival and differentiation of direct pathway striatonigral neurons during embryonic development. The downstream effectors of Isl1 in these processes are presently unknown. We show here that Foxo1, a transcription factor that has been implicated in cell survival, is expressed in striatal projection neurons (SPNs) that derive from the Isl1 lineage (i.e. direct pathway SPNs). Moreover, Isl1 conditional knockouts (cKOs) show a severe loss of Foxo1 expression at E15...
February 14, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28204875/repression-of-blade-on-petiole-genes-by-knox-homeodomain-protein-brevipedicellus-is-essential-for-differentiation-of-secondary-xylem-in-arabidopsis-root
#17
Natalie Woerlen, Gamalat Allam, Adina Popescu, Laura Corrigan, Véronique Pautot, Shelley R Hepworth
Repression of boundary genes by KNOTTED1-like homeodomain transcription factor BREVIPEDICELLUS promotes the differentiation of phase II secondary xylem in Arabidopsis roots. Plant growth and development relies on the activity of meristems. Boundaries are domains of restricted growth that separate forming organs and the meristem. Class I KNOX homeodomain transcription factors are important regulators of meristem maintenance. Members of this class including BREVIDICELLUS also called KNOTTED-LIKE FROM ARABIDOPSIS THALIANA1 (BP/KNAT1) fulfill this function in part by spatially regulating boundary genes...
February 15, 2017: Planta
https://www.readbyqxmd.com/read/28199838/islet-coordinately-regulates-motor-axon-guidance-and-dendrite-targeting-through-the-frazzled-dcc-receptor
#18
Celine Santiago, Greg J Bashaw
Motor neuron axon targeting in the periphery is correlated with the positions of motor neuron inputs in the CNS, but how these processes are coordinated to form a myotopic map remains poorly understood. We show that the LIM homeodomain factor Islet (Isl) controls targeting of both axons and dendrites in Drosophila motor neurons through regulation of the Frazzled (Fra)/DCC receptor. Isl is required for fra expression in ventrally projecting motor neurons, and isl and fra mutants have similar axon guidance defects...
February 14, 2017: Cell Reports
https://www.readbyqxmd.com/read/28179318/rearrangement-of-the-chromatin-organizer-special-at-rich-binding-protein-1-gene-satb1-resulting-from-a-t-3-5-p24-q14-chromosomal-translocation-in-acute-myeloid-leukemia
#19
Synne Torkildsen, Marta Brunetti, Ludmila Gorunova, Signe Spetalen, Klaus Beiske, Sverre Heim, Ioannis Panagopoulos
BACKGROUND/AIM: New chromosomal aberrations continue to be reported in acute myeloid leukemias (AML). The addition of more cases with the same genetic characteristics would establish an acquired aberration as a recurrent change, help determine its prognostic significance, and can provide insight into the mechanisms of leukemogenesis in patients with these rare abnormalities. CASE REPORT: RNA-sequencing was performed on a patient with AML with the bone marrow karyotype 46,XY,t(3;5)(p24;q14)[5]/46,XY[10]...
2017: Anticancer Research
https://www.readbyqxmd.com/read/28174607/pitx3-dna-methylation-is-an-independent-predictor-of-overall-survival-in-patients-with-head-and-neck-squamous-cell-carcinoma
#20
Verena Sailer, Emily Eva Holmes, Heidrun Gevensleben, Diane Goltz, Freya Dröge, Alina Franzen, Jörn Dietrich, Glen Kristiansen, Friedrich Bootz, Andreas Schröck, Dimo Dietrich
BACKGROUND: Molecular biomarkers assisting risk-group assignment and subsequent treatment stratification are urgently needed for patients with squamous cell cancer of the head and neck region (HNSCC). Aberrant methylation is a frequent event in cancer and, therefore, a promising source for potential biomarkers. Here, the methylation status of the paired-like homeodomain transcription factor 3 (PITX3) was evaluated in HNSCC. METHODS: Using a quantitative real-time PCR, PITX3 methylation was assessed in a cohort of 326 HNSCC patients treated for localized or locally advanced disease (training cohort)...
2017: Clinical Epigenetics
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