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https://www.readbyqxmd.com/read/29627878/discovery-of-a-small-molecule-inhibitor-of-dvl-cxxc5-interaction-by-computational-approaches
#1
Songling Ma, Jiwon Choi, Xuemei Jin, Hyun-Yi Kim, Ji-Hye Yun, Weontae Lee, Kang-Yell Choi, Kyoung Tai No
The Wnt/β-catenin signaling pathway plays a significant role in the control of osteoblastogenesis and bone formation. CXXC finger protein 5 (CXXC5) has been recently identified as a negative feedback regulator of osteoblast differentiation through a specific interaction with Dishevelled (Dvl) protein. It was reported that targeting the Dvl-CXXC5 interaction could be a novel anabolic therapeutic target for osteoporosis. In this study, complex structure of Dvl PDZ domain and CXXC5 peptide was simulated with molecular dynamics (MD)...
April 7, 2018: Journal of Computer-aided Molecular Design
https://www.readbyqxmd.com/read/29540477/the-cellular-stress-proteins-chchd10-and-mnrr1-chchd2-partners-in-mitochondrial-and-nuclear-function-and-dysfunction
#2
Neeraja Purandare, Mallika Somayajulu, Maik Hüttemann, Lawrence I Grossman, Siddhesh Aras
Coiled-coil-helix-coiled-coil-helix domain-containing 10 (CHCHD10) and CHCHD2 (MNRR1) are homologous proteins with 58% sequence identity and belong to the twin CX9C family of proteins that mediate cellular stress responses. Despite the identification of several neurodegeneration-associated mutations in the CHCHD10 gene, few studies have assessed its physiological role. Here, we investigated CHCHD10's function as a regulator of oxidative phosphorylation in the mitochondria and the nucleus. We show that CHCHD10 co-purifies with cytochrome c oxidase (COX) and up-regulates COX activity by serving as a scaffolding protein required for MNRR1 phosphorylation, mediated by ARG (ABL proto-oncogene 2, non-receptor tyrosine kinase [ABL2])...
March 14, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29180230/glucocorticoids-genes-and-brain-function
#3
REVIEW
Grzegorz R Juszczak, Adrian M Stankiewicz
The identification of key genes in transcriptomic data constitutes a huge challenge. Our review of microarray reports revealed 88 genes whose transcription is consistently regulated by glucocorticoids (GCs), such as cortisol, corticosterone and dexamethasone, in the brain. Replicable transcriptomic data were combined with biochemical and physiological data to create an integrated view of the effects induced by GCs. The most frequently reported genes were Errfi1 and Ddit4. Their up-regulation was associated with the altered transcription of genes regulating growth factor and mTORC1 signaling (Gab1, Tsc22d3, Dusp1, Ndrg2, Ppp5c and Sesn1) and progression of the cell cycle (Ccnd1, Cdkn1a and Cables1)...
March 2, 2018: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/29036306/cxxc5-suppresses-hepatocellular-carcinoma-by-promoting-tgf-%C3%AE-induced-cell-cycle-arrest-and-apoptosis
#4
Xiaohua Yan, Jingyi Wu, Quanlong Jiang, Hao Cheng, Jing-Dong J Han, Ye-Guang Chen
Evading TGF-β-mediated growth inhibition is often associated with tumorigenesis in liver, including hepatocellular carcinoma (HCC). To better understand the functions and the underlying molecular mechanisms of TGF-β in HCC initiation and progression, we carried out transcriptome sequencing (RNA-Seq) to identify the target genes of TGF-β. CXXC5, a member of the CXXC-type zinc finger domain-containing protein family, was identified as a novel TGF-β target gene in Hep3B HCC cells. Knockdown of CXXC5 attenuated the expression of a substantial portion of TGF-β target genes and ameliorated TGF-β-induced growth inhibition or apoptosis of Hep3B cells, suggesting that CXXC5 is required for TGF-β-mediated inhibition of HCC progression...
September 19, 2017: Journal of Molecular Cell Biology
https://www.readbyqxmd.com/read/29027288/cxxc5-expression-in-prostate-cancer-implications-for-cancer-progression
#5
Ines Benedetti, Angelo M De Marzo, Jan Geliebter, Niradiz Reyes
Identification of genes specifically deregulated in prostate adenocarcinoma may lead to discovery of new oncogenes/tumour suppressors with clinical relevance for diagnosis, prognosis and/or therapy. CXXC5 is a gene encoding a retinoid-inducible nuclear factor, whose overexpression in breast tumours, metastatic malignant melanomas and papillary thyroid carcinoma has been recently reported. We previously found differential expression of CXXC5 transcripts in metastatic prostate cancer cell lines of both rat and human origin...
August 2017: International Journal of Experimental Pathology
https://www.readbyqxmd.com/read/28967390/the-negative-regulator-cxxc5-making-wnt-look-a-little-less%C3%A2-dishevelled
#6
Dongwon Kim, Luis A Garza
Wingless-related integration site (WNT)/β-catenin signaling regulates diverse physiological functions including tissue regeneration. Activation of WNT signaling can be inhibited by various agents. Lee et al. investigate the interaction of CXXC-type zinc finger protein 5 (CXXC5) with Dishevelled as one such negative regulator of WNT in hair follicle regeneration.
November 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28626218/molecular-characterization-of-ezh2-mutant-patients-with-myelodysplastic-myeloproliferative-neoplasms
#7
J Rinke, J P Müller, M F Blaess, A Chase, M Meggendorfer, V Schäfer, N Winkelmann, C Haferlach, N C P Cross, A Hochhaus, T Ernst
Mutations in the epigenetic regulator gene EZH2 are frequently observed in patients with myelodysplastic/myeloproliferative neoplasms (MDS/MPN; 10-13%) and are associated with a poor outcome. To gain more insight into EZH2 pathology, we sought to genetically characterize a cohort of 41 EZH2-mutated MDS/MPN patients using targeted deep next-generation sequencing (NGS), colony-forming progenitor assays and transcriptome analysis. Stable short hairpin RNA (shRNA)-mediated downregulation of EZH2 was performed in MDS-derived F-36P, MOLM-13 and OCI-M2 cells to study EZH2-specific changes...
September 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28595998/targeting-of-cxxc5-by-a-competing-peptide-stimulates-hair-regrowth-and-wound-induced-hair-neogenesis
#8
REVIEW
Soung-Hoon Lee, Seol Hwa Seo, Dong-Hwan Lee, Long-Quan Pi, Won-Soo Lee, Kang-Yell Choi
The Wnt/β-catenin pathway has been implicated in hair follicle development and hair regeneration in adults. We discovered that CXXC-type zinc finger protein 5 (CXXC5) is a negative regulator of the Wnt/β-catenin pathway involved in hair regrowth and wound-induced hair follicle neogenesis via an interaction with Dishevelled. CXXC5 was upregulated in miniaturized hair follicles and arrector pili muscles in human balding scalps. The inhibitory effects of CXXC5 on alkaline phosphatase activity and cell proliferation were demonstrated using human hair follicle dermal papilla cells...
November 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28436992/corrigendum-kank1-inhibits-cell-growth-by-inducing-apoptosis-through-regulating-cxxc5-in-human-malignant-peripheral-nerve-sheath-tumors
#9
Zhibin Cui, Yingjia Shen, Kenny H Chen, Suresh K Mittal, Jer-Yen Yang, GuangJun Zhang
No abstract text is available yet for this article.
April 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28416650/epigenetic-regulator-cxxc5-recruits-dna-demethylase-tet2-to-regulate-tlr7-9-elicited-ifn-response-in-pdcs
#10
Shixin Ma, Xiaoling Wan, Zihou Deng, Lei Shi, Congfang Hao, Zhenyuan Zhou, Chun Zhou, Yiyuan Fang, Jinghua Liu, Jing Yang, Xia Chen, Tiantian Li, Aiping Zang, Shigang Yin, Bin Li, Joel Plumas, Laurence Chaperot, Xiaoming Zhang, Guoliang Xu, Lubin Jiang, Nan Shen, Sidong Xiong, Xiaoming Gao, Yan Zhang, Hui Xiao
TLR7/9 signals are capable of mounting massive interferon (IFN) response in plasmacytoid dendritic cells (pDCs) immediately after viral infection, yet the involvement of epigenetic regulation in this process has not been documented. Here, we report that zinc finger CXXC family epigenetic regulator CXXC5 is highly expressed in pDCs, where it plays a crucial role in TLR7/9- and virus-induced IFN response. Notably, genetic ablation of CXXC5 resulted in aberrant methylation of the CpG-containing island (CGI) within the Irf7 gene and impaired IRF7 expression in steady-state pDCs...
May 1, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28184940/circular-rna-and-gene-expression-profiles-in-gastric-cancer-based-on-microarray-chip-technology
#11
COMPARATIVE STUDY
Weiguo Sui, Zhoufang Shi, Wen Xue, Minglin Ou, Ying Zhu, Jiejing Chen, Hua Lin, Fuhua Liu, Yong Dai
The aim of the present study was to screen gastric cancer (GC) tissue and adjacent tissue for differences in mRNA and circular (circRNA) expression, to analyze the differences in circRNA and mRNA expression, and to investigate the circRNA expression in gastric carcinoma and its mechanism. circRNA and mRNA differential expression profiles generated using Agilent microarray technology were analyzed in the GC tissues and adjacent tissues. qRT-PCR was used to verify the differential expression of circRNAs and mRNAs according to the interactions between circRNAs and miRNAs as well as the possible existence of miRNA and mRNA interactions...
March 2017: Oncology Reports
https://www.readbyqxmd.com/read/28067315/kank1-inhibits-cell-growth-by-inducing-apoptosis-though-regulating-cxxc5-in-human-malignant-peripheral-nerve-sheath-tumors
#12
Zhibin Cui, Yingjia Shen, Kenny H Chen, Suresh K Mittal, Jer-Yen Yang, GuangJun Zhang
Malignant peripheral nerve sheath tumors (MPNSTs) are a type of rare sarcomas with a poor prognosis due to its highly invasive nature and limited treatment options. Currently there is no targeted-cancer therapy for this type of malignancy. Thus, it is important to identify more cancer driver genes that may serve as targets of cancer therapy. Through comparative oncogenomics, we have found that KANK1 was a candidate tumor suppressor gene (TSG) for human MPNSTs. Although KANK1 is known as a cytoskeleton regulator, its tumorigenic function in MPNSTs remains largely unknown...
January 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/27932247/crystal-structure-of-the-pdz-domain-of-mouse-dishevelled-1-and-its-interaction-with-cxxc5
#13
Inhwan Lee, Sooho Choi, Ji-Hye Yun, Seol Hwa Seo, Sehee Choi, Kang-Yell Choi, Weontae Lee
Dishevelled (Dvl) plays a crucial role in Wnt signaling by interacting with membrane-bound receptors and downstream molecules through its PDZ domain. CXXC5 is one of the key molecules that interacts with Dvl and negatively regulates the Wnt/β-catenin pathway in osteoblast differentiation. Recently, the Dvl-CXXC5 interaction has been identified as an excellent target for osteoporosis treatment. Therefore, it is desirable to have detailed structural information for the Dvl-CXXC5 interaction. Although solution structures of the Dvl1 PDZ domain have been reported, a high-resolution crystal structure would provide detailed sidechain information that is essential for drug development...
April 8, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27886276/estradiol-estrogen-receptor-%C3%AE-mediates-the-expression-of-the-cxxc5-gene-through-the-estrogen-response-element-dependent-signaling-pathway
#14
Pelin Yaşar, Gamze Ayaz, Mesut Muyan
17β-estradiol (E2), the primary circulating estrogen hormone, mediates physiological and pathophysiological functions of breast tissue mainly through estrogen receptor α (ERα). Upon binding to E2, ERα modulates the expression of target genes involved in the regulation of cellular proliferation primarily through interactions with specific DNA sequences, estrogen response elements (EREs). Our previous microarray results suggested that E2-ERα modulates CXXC5 expression. Because of the presence of a zinc-finger CXXC domain (ZF-CXXC), CXXC5 is considered to be a member of the ZF-CXXC family, which binds to non-methylated CpG dinucleotides...
November 25, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27077543/cxxc5-is-required-for-cardiac-looping-relating-to-tgf%C3%AE-signaling-pathway-in-zebrafish
#15
Xiyang Peng, Guanming Li, Yuequn Wang, Jian Zhuang, Rong Luo, Jimei Chen, Fa Chen, Yan Shi, Jiani Li, Zuoqiong Zhou, Xiaoyang Mo, Xianchu Liu, Wuzhou Yuan, Qun Zeng, Yongqing Li, Zhigang Jiang, Yongqi Wan, Xiangli Ye, Wei Xu, Xijun Wang, Xiongwei Fan, Ping Zhu, Xiushan Wu, Yun Deng
BACKGROUND: CXXC-type zinc-finger protein CXXC5 has been reported to be associated with the development of cardiovascular disease. Recently, through signaling pathway screening we found that CXXC5 activated Tgfβ and myocardial differentiation signaling pathways simultaneously. Although the physiological and pathological function of CXXC5 in many organs has been well elucidated, its function in heart remains unclear. METHODS AND RESULTS: Here, we found that zebrafish CXXC5 and SMAD were interacting through ZF-CXXC and MH1 domain...
July 1, 2016: International Journal of Cardiology
https://www.readbyqxmd.com/read/26944478/retroviral-insertional-mutagenesis-identifies-the-del-5q-genes-cxxc5-tifab-and-etf1-as-well-as-the-wnt-pathway-as-potential-targets-in-del-5q-myeloid-neoplasms
#16
LETTER
Angela Stoddart, Zhijian Qian, Anthony A Fernald, Rachel J Bergerson, Jianghong Wang, Theodore Karrison, John Anastasi, Elizabeth T Bartom, Aaron L Sarver, Megan E McNerney, David A Largaespada, Michelle M Le Beau
No abstract text is available yet for this article.
June 2016: Haematologica
https://www.readbyqxmd.com/read/26941261/small-molecule-inhibitors-of-the-dishevelled-cxxc5-interaction-are-new-drug-candidates-for-bone-anabolic-osteoporosis-therapy
#17
Hyun-Yi Kim, Sehee Choi, Ji-Hye Yoon, Hwan Jung Lim, Hyuk Lee, Jiwon Choi, Eun Ji Ro, Jung-Nyoung Heo, Weontae Lee, Kyoung Tai No, Kang-Yell Choi
Bone anabolic agents promoting bone formation and rebuilding damaged bones would ideally overcome the limitations of anti-resorptive therapy, the current standard prescription for osteoporosis. However, the currently prescribed parathyroid hormone (PTH)-based anabolic drugs present limitations and adverse effects including osteosarcoma during long-term use. Also, the antibody-based anabolic drugs that are currently being developed present the potential limits in clinical application typical of macromolecule drugs...
April 1, 2016: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/26689247/gene-expression-profiling-of-prostate-cancer-associated-genes-identifies-fibromodulin-as-potential-novel-biomarker-for-prostate-cancer
#18
Alfonso Bettin, Ismael Reyes, Niradiz Reyes
BACKGROUND: The aim of this study was to evaluate the gene expression profiles of a set of prostate cancer-associated genes in prostate cancer cell lines, to determine their association with different cancer phenotypes and identify potential novel biomarkers for this disease. METHODS: Quantitative real-time PCR was used to determine the expression profiles of 21 prostate cancer-associated genes in the human prostate cancer cell lines PC-3 and LNCaP, using the nontumorigenic cell line PWR-1E as control cell line...
May 28, 2016: International Journal of Biological Markers
https://www.readbyqxmd.com/read/26462610/cxxc5-plays-a-role-as-a-transcription-activator-for-myelin-genes-on-oligodendrocyte-differentiation
#19
Mi-Yeon Kim, Hyun-Yi Kim, Jiso Hong, Daesoo Kim, Hyojung Lee, Eunji Cheong, Yangsin Lee, Jürgen Roth, Dong Goo Kim, Do Sik Min, Kang-Yell Choi
Myelination in corpus callosum plays important role for normal brain functions by transferring neurological information between various brain regions. However, the factors controlling expression of myelin genes in myelination are poorly understood. Here, CXXC5, a recently identified protein with CXXC-type zinc finger DNA binding motif, was characterized as a transcriptional activator of major myelin genes. We identified expression of CXXC5 expression was increased by Wnt/β-catenin signaling. CXXC5 specifically expressed in the white matter induced expression of myelin genes through the direct binding of CXXC DNA-binding motif of CXXC5 on the MBP promoter...
March 2016: Glia
https://www.readbyqxmd.com/read/26436701/length-of-paternal-lifespan-is-manifested-in-the-dna-methylome-of-their-nonagenarian-progeny
#20
Saara Marttila, Laura Kananen, Juulia Jylhävä, Tapio Nevalainen, Antti Hervonen, Marja Jylhä, Mikko Hurme
The heritability of lifespan is 20-30%, but only a few genes associated with longevity have been identified. To explain this discrepancy, the inheritance of epigenetic features, such as DNA methylation, have been proposed to contribute to the heritability of lifespan.We investigated whether parental lifespan is associated with DNA methylation profile in nonagenarians. A regression model, adjusted for differences in blood cell proportions, identified 659 CpG sites where the level of methylation was associated with paternal lifespan...
October 13, 2015: Oncotarget
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