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Linnea A Weiss, Marta Nieto
Cux1 and Cux2 are the vertebrate members of a family of homeodomain transcription factors (TF) containing Cut repeat DNA-binding sequences. Perturbation of their expression has been implicated in a wide variety of diseases and disorders, ranging from cancer to autism spectrum disorder (ASD). Within the nervous system, both genes are expressed during neurogenesis and in specific neuronal subpopulations. Their role during development and circuit specification is discussed here, with a particular focus on the cortex where their restricted expression in pyramidal neurons of the upper layers appears to be responsible for many of the specialized functions of these cells, and where their functions have been extensively investigated...
March 5, 2018: Brain Research
Jan Smetana, Jan Oppelt, Martin Štork, Luděk Pour, Petr Kuglík
Background: Catastrophic chromosomal event known as chromothripsis was proven to be a significant hallmark of poor prognosis in several cancer diseases. While this phenomenon is very rare in among multiple myeloma (MM) patients, its presence in karyotype is associated with very poor prognosis. Case presentation: In our case, we report a 62 year female patient with rapid progression of multiple myeloma (MM) into extramedullary disease and short overall survival (OS = 23 months)...
2018: Molecular Cytogenetics
Yao Fei, Yajie Xiong, Xiao Shen, Yifan Zhao, Ying Zhu, Long Wang, Zhongqin Liang
Cathepsin L (CTSL) is a lysosomal cysteine protease overexpressed and secreted by tumor cells. Our previous study found that CTSL was involved in ionizing radiation (IR)-induced epithelial-mesenchymal transition (EMT) and the increase of glioma invasion and migration. However, the mechanisms by which CTSL promoted this IR-induced glioma migration and invasion remained unclear. In this study, we demonstrated that IR reduced glycogen synthase kinase-3β (GSK-3β) activity, via the CTSL-mediated phosphorylation of its serine-9 residue, in U251 cells...
January 10, 2018: Cellular Signalling
Long Wang, Yifan Zhao, Yajie Xiong, Wenjuan Wang, Yao Fei, Caihong Tan, Zhongqin Liang
K-ras mutation is involved in cancer progression including invasion and migration, but the underlying mechanism is not yet clear. Cathepsin L is a lysosomal cysteine protease and has recently been associated with invasion and migration in human cancers when it is overexpressed. Our recent studies have shown that ionizing radiation (IR) enhanced expression of cathepsin L and increased invasion and migration of tumor cells, but the molecular mechanism is still unclear. In the present study, the effects of K-ras mutation and IR induced invasion and migration of lung cancer as well as the underlying mechanisms were investigated both in vitro and in vivo...
December 12, 2017: Experimental Cell Research
Yan-Xia Ma, Xiu-Li Wang, Jian-Quan Chen, Bin Li, Eun-Mi Hur, Saijilafu
Glycogen synthase kinases 3 (GSK3) α and β are expressed in the nervous system, and disruption of GSK3 signaling has been implicated in a wide range of neurodevelopmental and psychiatric disorders. Although several studies have established a role of GSK3 signaling in the nervous system, much less is known about isoform-specific functions. Here, we have examined the role of GSK3α and GSK3β in the developing neocortex by performing in utero electroporation with specific small interfering RNAs targeting each isoform...
2017: Frontiers in Molecular Neuroscience
Dongkyoon Kim, Christian Schmidt, Mark A Brown, Haley Tucker
Arid3a/Bright/Dril1 is a B cell-specific transactivator that regulates immunoglobulin heavy chain (IgH) gene transcription by binding promoter and enhancer-associated matrix attachment regions (MARs) within the IgH gene locus. Promoter MAR-mediated Arid3a transactivation is antagonized by direct competition of MAR binding by Cux1/CDP-a ubiquitously expressed repressor originally termed NF-μNR. We report that the NF-μNR complex includes Arid3a in B cells but not in non-B cells through mobility shift assays...
December 10, 2017: Diseases (Basel)
Andreas Giannakou, Robert J Sicko, Wei Zhang, Paul Romitti, Marilyn L Browne, Michele Caggana, Lawrence C Brody, Laura Jelliffe-Pawlowski, Gary M Shaw, Denise M Kay, James L Mills
BACKGROUND: Ebstein anomaly (EA) is a rare congenital defect characterized by apical displacement of the septal tricuspid leaflets and atrialization of the right ventricle. The etiology of EA is unclear; however, recurrence in families and the association of EA with genetic syndromes and copy number variants (CNVs) suggest a genetic component. OBJECTIVE: We performed a population-based study to search for recurrent and novel CNVs in a previously unreported set of EA cases...
2017: PloS One
Abinaya Chandrasekaran, Hasan X Avci, Anna Ochalek, Lone N Rösingh, Kinga Molnár, Lajos László, Tamás Bellák, Annamária Téglási, Krisztina Pesti, Arpad Mike, Phetcharat Phanthong, Orsolya Bíró, Vanessa Hall, Narisorn Kitiyanant, Karl-Heinz Krause, Julianna Kobolák, András Dinnyés
Neural progenitor cells (NPCs) from human induced pluripotent stem cells (hiPSCs) are frequently induced using 3D culture methodologies however, it is unknown whether spheroid-based (3D) neural induction is actually superior to monolayer (2D) neural induction. Our aim was to compare the efficiency of 2D induction with 3D induction method in their ability to generate NPCs, and subsequently neurons and astrocytes. Neural differentiation was analysed at the protein level qualitatively by immunocytochemistry and quantitatively by flow cytometry for NPC (SOX1, PAX6, NESTIN), neuronal (MAP2, TUBB3), cortical layer (TBR1, CUX1) and glial markers (SOX9, GFAP, AQP4)...
October 14, 2017: Stem Cell Research
Simran Kaur, Zubaidah M Ramdzan, Marie-Christine Guiot, Li Li, Lam Leduy, Dindial Ramotar, Siham Sabri, Bassam Abdulkarim, Alain Nepveu
Background: CUX1, which encodes an auxiliary factor in base excision repair, resides on 7q22.1, the most frequently and highly amplified chromosomal region in glioblastomas. The resistance of glioblastoma cells to the mono-alkylating agent temozolomide is determined to some extent by the activity of the apurinic/apyrimidinic endonuclease 1, APE1. Methods: To monitor the effect of CUX1 and its CUT domains on APE1 activity, DNA repair assays were performed with purified proteins and cell extracts...
September 26, 2017: Neuro-oncology
Roxanne Latreille, Raphaëlle Servant, Mathieu Darsigny, Sébastien Marcoux, Christine Jones, Nathalie Perreault, François Boudreau
Intestinal epithelial cells form a protective barrier in limiting gut luminal content potentially harmful to the host. Upon gut epithelium injury, several signals instruct epithelial cells to undergo a rapid healing process. Defects in this process induce inflammatory responses and can further evolve into chronic gut inflammatory diseases. We previously identified the transcription factor CUX1 as crucial for protecting against experimental colitis in mice. However, the precise molecular mechanisms by which CUX1 intervenes during this biological process are unknown...
December 2017: Biochimica et Biophysica Acta
Yuling Zhou, Brett D Hambly, Craig S McLachlan
This review examines the biology of the Fat mass- and obesity-associated gene (FTO), and the implications of genetic association of FTO SNPs with obesity and genetic aging. Notably, we focus on the role of FTO in the regulation of methylation status as possible regulators of weight gain and genetic aging. We present a theoretical review of the FTO gene with a particular emphasis on associations with UCP2, AMPK, RBL2, IRX3, CUX1, mTORC1 and hormones involved in hunger regulation. These associations are important for dietary behavior regulation and cellular nutrient sensing via amino acids...
September 1, 2017: Journal of Biomedical Science
Odessa R Yabut, Hui Xuan Ng, Gloria Fernandez, Keejung Yoon, Jeremy Kuhn, Samuel J Pleasure
Neural progenitors in the embryonic neocortex must be tightly regulated in order to generate the correct number and projection neuron subtypes necessary for the formation of functional neocortical circuits. In this study, we show that the intracellular protein Suppressor of Fused (Sufu) regulates the proliferation of intermediate progenitor (IP) cells at later stages of corticogenesis to affect the number of Cux1+ upper layer neurons in the postnatal neocortex. This correlates with abnormal levels of the repressor form of Gli3 (Gli3R) and the ectopic expression of Patched 1 (Ptch1), a Sonic Hedgehog (Shh) target gene...
December 2016: Journal of Developmental Biology
Binu Porath, Safia Livingston, Erica L Andres, Alexandra M Petrie, Joshua C Wright, Anna E Woo, Carol G Carlton, Richard Baybutt, Gregory B Vanden Heuvel
Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common monogenic hereditary disorders in humans characterized by fluid-filled cysts, primarily in the kidneys. Cux1, a cell cycle regulatory gene highly expressed during kidney development, is elevated in the cyst-lining cells of Pkd1 mutant mice, and in human ADPKD cells. However, forced expression of Cux1 is insufficient to induce cystic disease in transgenic mice or to induce rapid cyst formation after cilia disruption in the kidneys of adult mice...
October 1, 2017: American Journal of Physiology. Renal Physiology
Liza J Burton, Veronica Henderson, Latiffa Liburd, Valerie A Odero-Marah
Several recent studies have highlighted an additional unexpected localization and site of action for Cathepsin L (Cat L) protease within the nucleus in breast, colon and prostate cancer, however, its role in the nucleus was unclear. It was proposed to mediate proteolytic processing of the transcription factor CCAAT-displacement protein/cut homeobox transcription factor (Cux1) from the full-length p200 isoform to generate the p110 and p90 isoforms, of which the p110 isoform was shown to act as a cell cycle regulator to accelerate entry into the S phase...
September 9, 2017: Biochemical and Biophysical Research Communications
Salem A El-Aarag, Amal Mahmoud, Medhat H Hashem, Hatem Abd Elkader, Alaa E Hemeida, Mahmoud ElHefnawi
BACKGROUND: Lung cancer is a leading cause of cancer-related death worldwide and is the most commonly diagnosed cancer. Like other cancers, it is a complex and highly heterogeneous disease involving multiple signaling pathways. Identifying potential therapeutic targets is critical for the development of effective treatment strategies. METHODS: We used a systems biology approach to identify potential key regulatory factors in smoking-induced lung cancer. We first identified genes that were differentially expressed between smokers with normal lungs and those with cancerous lungs, then integrated these differentially expressed genes (DEGs) with data from a protein-protein interaction database to build a network model with functional modules for pathway analysis...
June 7, 2017: BMC Medical Genomics
Hoe-Su Jeong, Jinhyuk Bhin, Hyung Joon Kim, Daehee Hwang, Dong Ryul Lee, Kye-Seong Kim
Spermatogonial stem cells (SSCs) are germline stem cells located along the basement membrane of seminiferous tubules in testes. Recently, SSCs were shown to be reprogrammed into multipotent SSCs (mSSCs). However, both the key factors and biological networks underlying this reprogramming remain elusive. Here, we present transcriptional regulatory networks (TRNs) that control cellular processes related to the SSC-to-mSSC reprogramming. Previously, we established intermediate SSCs (iSSCs) undergoing the transition to mSSCs and generated gene expression profiles of SSCs, iSSCs and mSSCs...
April 14, 2017: Experimental & Molecular Medicine
Robert K Arthur, Ningfei An, Saira Khan, Megan E McNerney
One third of tumor suppressors are haploinsufficient transcriptional regulators, yet it remains unknown how a 50% reduction of a transcription factor is translated at the cis-regulatory level into a malignant transcriptional program. We studied CUX1, a haploinsufficient transcription factor that is recurrently mutated in hematopoietic and solid tumors. We determined CUX1 DNA-binding and target gene regulation in the wildtype and haploinsufficient states. CUX1 binds with transcriptional activators and cohesin at distal enhancers across three different human cell types...
June 20, 2017: Nucleic Acids Research
Zubaidah M Ramdzan, Vasudeva Ginjala, Jordan B Pinder, Dudley Chung, Caroline M Donovan, Simran Kaur, Lam Leduy, Graham Dellaire, Shridar Ganesan, Alain Nepveu
Ionizing radiation generates a broad spectrum of oxidative DNA lesions, including oxidized base products, abasic sites, single-strand breaks and double-strand breaks. The CUX1 protein was recently shown to function as an auxiliary factor that stimulates enzymatic activities of OGG1 through its CUT domains. In the present study, we investigated the requirement for CUX1 and OGG1 in the resistance to radiation. Cancer cell survival following ionizing radiation is reduced by CUX1 knockdown and increased by higher CUX1 expression...
March 21, 2017: Oncotarget
Lucas T Gray, Zizhen Yao, Thuc Nghi Nguyen, Tae Kyung Kim, Hongkui Zeng, Bosiljka Tasic
Mammalian cortex is a laminar structure, with each layer composed of a characteristic set of cell types with different morphological, electrophysiological, and connectional properties. Here, we define chromatin accessibility landscapes of major, layer-specific excitatory classes of neurons, and compare them to each other and to inhibitory cortical neurons using the Assay for Transposase-Accessible Chromatin with high-throughput sequencing (ATAC-seq). We identify a large number of layer-specific accessible sites, and significant association with genes that are expressed in specific cortical layers...
January 23, 2017: ELife
Elaine Fletcher, Jean Wade, Petrina A Georgala, Trudi L Gillespie, David J Price, Elizabeth Pilley, Julie-Clare Becher
BACKGROUND: The mammalian cerebral cortex forms in an inside-out manner, establishing deep cortical layers before superficial layers and is regulated by transcription factors which influence cell differentiation. Preterm birth interrupts the trajectory of normal neurodevelopment and adverse perinatal exposures have been implicated in cortical injury. We hypothesise that growth restriction (GR) and fluctuating hyperoxia (ΔO2) impair cortical laminar development. METHODS: Sprague-Dawley rats received 18% (non-restricted, NR) or 9% (growth restricted, GR) protein diet from E15-P7...
March 2017: Annals of Anatomy, Anatomischer Anzeiger: Official Organ of the Anatomische Gesellschaft
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