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https://www.readbyqxmd.com/read/29217659/rock-dependent-phosphorylation-of-nup62-regulates-p63-nuclear-transport-and-squamous-cell-carcinoma-proliferation
#1
Masaharu Hazawa, De-Chen Lin, Akiko Kobayashi, Yan-Yi Jiang, Liang Xu, Firli Rahmah Primula Dewi, Mahmoud Shaaban Mohamed, Hartono, Mitsutoshi Nakada, Makiko Meguro-Horike, Shin-Ichi Horike, H Phillip Koeffler, Richard W Wong
p63, more specifically its ΔNp63α isoform, plays essential roles in squamous cell carcinomas (SCCs), yet the mechanisms controlling its nuclear transport remain unknown. Nucleoporins (NUPs) are a family of proteins building nuclear pore complexes (NPC) and mediating nuclear transport across the nuclear envelope. Recent evidence suggests a cell type-specific function for certain NUPs; however, the significance of NUPs in SCC biology remains unknown. In this study, we show that nucleoporin 62 (NUP62) is highly expressed in stratified squamous epithelia and is further elevated in SCCs...
December 7, 2017: EMBO Reports
https://www.readbyqxmd.com/read/29209056/transcription-regulation-by-the-mediator-complex
#2
REVIEW
Julie Soutourina
Alterations in the regulation of gene expression are frequently associated with developmental diseases or cancer. Transcription activation is a key phenomenon in the regulation of gene expression. In all eukaryotes, mediator of RNA polymerase II transcription (Mediator), a large complex with modular organization, is generally required for transcription by RNA polymerase II, and it regulates various steps of this process. The main function of Mediator is to transduce signals from the transcription activators bound to enhancer regions to the transcription machinery, which is assembled at promoters as the preinitiation complex (PIC) to control transcription initiation...
December 6, 2017: Nature Reviews. Molecular Cell Biology
https://www.readbyqxmd.com/read/29207637/wheat-germ-agglutinin-induced-paraptosis-like-cell-death-and-protective-autophagy-is-mediated-by-autophagy-linked-fyve-inhibition
#3
Tsung Lin Tsai, Hao Chen Wang, Chun Hua Hung, Peng Chan Lin, Yi San Lee, Helen H W Chen, Wu Chou Su
Wheat germ agglutinin (WGA) is a lectin that specifically binds cell surface glycoproteins and disrupts nuclear pore complex function through its interaction with POM121. Our data indicate WGA induces paraptosis-like cell death without caspase activation. We observed the main features of paraptosis, including cytoplasmic vacuolation, endoplasmic reticulum dilation and increased ER stress, and the unfolded protein response in WGA-treated cervical carcinoma cells. Conversion of microtubule-associated protein I light chain 3 (LC3-I) into LC3-II and punctuate formation suggestive of autophagy were observed in WGA-treated cells...
October 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/29207257/forcing-entry-into-the-nucleus
#4
Alexis Lomakin, Guilherme Nader, Matthieu Piel
Nuclear pore complexes tightly regulate nucleo-cytoplasmic transport, controlling the nuclear concentration of several transcription factors. In a recent issue of Cell, Elosegui-Artola et al. (2017) show that nuclear deformation modulates the nuclear entry rates of YAP/TAZ via nuclear pore stretching, clarifying how forces affect gene transcription.
December 4, 2017: Developmental Cell
https://www.readbyqxmd.com/read/29207128/nr4a1-induced-increase-in-the-sensitivity-of-a-human-gastric-cancer-line-to-tnf%C3%AE-mediated-apoptosis-is-associated-with-the-inhibition-of-jnk-parkin-dependent-mitophagy
#5
Hongzhu Yan, Feng Xiao, Jue Zou, Chengmin Qiu, Weiwei Sun, Minmin Gu, Li Zhang
Tumor necrosis factor α (TNFα)-based immunotherapy is the vital host defense system against the progression of gastric cancer (GC) as a pro-inflammatory and pro-apoptotic cytokine. However, resistance limits its therapeutic efficiency. Therefore, an increasing number of studies are focusing on the development of drugs or methods with which to enhance the treatment efficacy of TNFα. Nuclear receptor subfamily 4 group A member 1 (NR4A1) has been shown to exert antitumor effects through several mechanisms, such as by inhibiting proliferation, as well as pro-apoptotic and potent pro-oxidant effects...
December 4, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29203613/nfe2l1-silenced-insulinoma-cells-acquire-aggressiveness-and-chemo-resistance
#6
Jingqi Fu, Hongzhi Zheng, Qi Cui, Chengjie Chen, Simeng Bao, Jing Sun, Lu Li, Bei Yang, Huihui Wang, Yongyong Hou, Yuanyuan Xu, Yuanhong Xu, Qiang Zhang, Jingbo Pi
The transcription factor nuclear factor erythroid 2 like 1 (NFE2L1 or NRF1) is involved in various critical cell processes such as maintenance of ubiquitin-proteasome system and regulation of the cellular antioxidant response. We previously determined that pancreatic β-cell-specific Nfe2l1-knockout mice had hyperinsulinemia, and that silencing of Nfe2l1 in mouse islets or MIN6 insulinoma β-cells induced elevated basal insulin release and altered glucose metabolism. Hypoglycemia is a major issue with aggressive insulinomas, although a role of NFE2L1 in this pathology is not defined...
December 4, 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/29197695/probing-numerical-laplace-inversion-methods-for-two-and-three-site-molecular-exchange-between-interconnected-pore-structures
#7
Emilia V Silletta, María B Franzoni, Gustavo A Monti, Rodolfo H Acosta
Two-dimension (2D) Nuclear Magnetic Resonance relaxometry experiments are a powerful tool extensively used to probe the interaction among different pore structures, mostly in inorganic systems. The analysis of the collected experimental data generally consists of a 2D numerical inversion of time-domain data where T2-T2 maps are generated. Through the years, different algorithms for the numerical inversion have been proposed. In this paper, two different algorithms for numerical inversion are tested and compared under different conditions of exchange dynamics; the method based on Butler-Reeds-Dawson (BRD) algorithm and the fast-iterative shrinkage-thresholding algorithm (FISTA) method...
November 30, 2017: Journal of Magnetic Resonance
https://www.readbyqxmd.com/read/29196813/sense-encoded-poly-gr-dipeptide-repeat-proteins-correlate-to-neurodegeneration-and-uniquely-co-localize-with-tdp-43-in-dendrites-of-repeat-expanded-c9orf72-amyotrophic-lateral-sclerosis
#8
Shahram Saberi, Jennifer E Stauffer, Jie Jiang, Sandra Diaz Garcia, Amy E Taylor, Derek Schulte, Takuya Ohkubo, Cheyenne L Schloffman, Marcus Maldonado, Michael Baughn, Maria J Rodriguez, Don Pizzo, Don Cleveland, John Ravits
Hexanucleotide repeat expansions in C9orf72 are the most common genetic cause of amyotrophic lateral sclerosis (C9 ALS). The main hypothesized pathogenic mechanisms are C9orf72 haploinsufficiency and/or toxicity from one or more of bi-directionally transcribed repeat RNAs and their dipeptide repeat proteins (DPRs) poly-GP, poly-GA, poly-GR, poly-PR and poly-PA. Recently, nuclear import and/or export defects especially caused by arginine-containing poly-GR or poly-PR have been proposed as significant contributors to pathogenesis based on disease models...
December 1, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/29195049/a-solid-state-conceptualization-of-information-transfer-from-gene-to-message-to-protein
#9
Masato Kato, Steven L McKnight
In this review, we describe speculative ideas and early stage research concerning the flow of genetic information from the nuclear residence of genes to the disparate, cytoplasmic sites of protein synthesis. We propose that this process of information transfer is meticulously guided by transient structures formed from protein segments of low sequence complexity/intrinsic disorder. These low complexity domains are ubiquitously associated with regulatory proteins that control gene expression and RNA biogenesis, but they are also found in the central channel of nuclear pores, the nexus points of intermediate filament assembly, and the locations of action of other well-studied cellular proteins and pathways...
December 1, 2017: Annual Review of Biochemistry
https://www.readbyqxmd.com/read/29194456/tools-for-retargeting-proteins-within-aspergillus-nidulans
#10
Subbulakshmi Suresh, Leymaan Abdurehman, Aysha H Osmani, Stephen A Osmani
Endogenously tagging proteins with green fluorescent protein (GFP) enables the visualization of the tagged protein using live cell microscopy. GFP-tagging is widely utilized to study biological processes in model experimental organisms including filamentous fungi such as Aspergillus nidulans. Many strains of A. nidulans have therefore been generated with different proteins endogenously tagged with GFP. To further enhance experimental approaches based upon GFP-tagging, we have adapted the GFP Binding Protein (GBP) system for A...
2017: PloS One
https://www.readbyqxmd.com/read/29192710/dynamical-properties-of-emim-scn-confined-in-a-sio2-matrix-by-means-of-1h-nmr-relaxometry
#11
Danuta Kruk, Milosz Wojciechowski, Yogendra Lal Verma, Sujeet Kumar Chaurasia, Rajendra Kumar Singh
1H nuclear magnetic resonance relaxometry is applied to investigate the translational and rotational dynamics of ionogels composed of an ionic liquid (IL): 1-ethyl-3-methyl-imidazolium-thiocyanate (EMIM-SCN) confined in a nanoporous SiO2 matrix. The relaxation studies were performed in the frequency range of 4 kHz-40 MHz and the temperature range of 223-248 K for different concentrations of the IL; the ratio (no. of moles of IL/no. of moles of SiO2) yields: 1/2, 3/5 and 7/10. A thorough analysis of this large set of experimental data was performed assuming the existence of two fractions of the liquid: a core fraction (near the pore center) and a surface fraction (near the confining walls)...
December 1, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/29186574/torsina-dysfunction-causes-persistent-neuronal-nuclear-pore-defects
#12
Samuel S Pappas, Chun-Chi Liang, Sumin Kim, CheyAnne O Rivera, William T Dauer
A critical challenge to deciphering the pathophysiology of neurodevelopmental disease is identifying which of the myriad abnormalities that emerge during CNS maturation persist to contribute to long-term brain dysfunction. Childhood-onset dystonia caused by a loss-of-function mutation in the AAA+ protein torsinA exemplifies this challenge. Neurons lacking torsinA develop transient nuclear envelope (NE) malformations during CNS maturation, but no NE defects are described in mature torsinA null neurons. We find that during postnatal CNS maturation torsinA null neurons develop mislocalized and dysfunctional nuclear pore complexes (NPC) that lack NUP358, normally added late in NPC biogenesis...
November 24, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/29180826/persistent-inhibition-of-pore-based-cell-migration-by-sub-toxic-doses-of-miuraenamide-an-actin-filament-stabilizer
#13
Christina Moser, Daniel Rüdiger, Florian Förster, Julia von Blume, Peng Yu, Bernhard Kuster, Uli Kazmaier, Angelika M Vollmar, Stefan Zahler
Opposed to tubulin-binding agents, actin-binding small molecules have not yet become part of clinical tumor treatment, most likely due to the fear of general cytotoxicity. Addressing this problem, we investigated the long-term efficacy of sub-toxic doses of miuraenamide, an actin filament stabilizing natural compound, on tumor cell (SKOV3) migration. No cytotoxic effects or persistent morphological changes occurred at a concentration of miuraenamide of 20 nM. After 72 h treatment with this concentration, nuclear stiffness was increased, causing reduced migration through pores in a Boyden chamber, while cell migration and chemotaxis per se were unaltered...
November 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29179637/cone-dystrophy-and-ectopic-synaptogenesis-in-a-cacna1f-loss-of-function-model-of-congenital-stationary-night-blindness-csnb2a
#14
D M Waldner, N C Giraldo Sierra, S Bonfield, L Nguyen, I S Dimopoulos, Y Sauvé, W K Stell, N T Bech-Hansen
Congenital stationary night blindness 2A (CSNB2A) is an X-linked retinal disorder, characterized by phenotypically variable signs and symptoms of impaired vision. CSNB2A is due to mutations in CACNA1F, which codes for the pore-forming α1F subunit of a L-type voltage-gated calcium channel, Cav1.4. Mouse models of CSNB2A, used for characterizing the effects of various Cacna1f mutations, have revealed greater severity of defects than in human CSNB2A. Specifically, Cacna1f-knockout mice show an apparent lack of visual function, gradual retinal degeneration, and disruption of photoreceptor synaptic terminals...
November 28, 2017: Channels
https://www.readbyqxmd.com/read/29176624/a-statistical-image-analysis-framework-for-pore-free-islands-derived-from-heterogeneity-distribution-of-nuclear-pore-complexes
#15
Yasuhiro Mimura, Satoko Takemoto, Taro Tachibana, Yutaka Ogawa, Masaomi Nishimura, Hideo Yokota, Naoko Imamoto
Nuclear pore complexes (NPCs) maintain cellular homeostasis by mediating nucleocytoplasmic transport. Although cyclin-dependent kinases (CDKs) regulate NPC assembly in interphase, the location of NPC assembly on the nuclear envelope is not clear. CDKs also regulate the disappearance of pore-free islands, which are nuclear envelope subdomains; this subdomain gradually disappears with increase in homogeneity of the NPC in response to CDK activity. However, a causal relationship between pore-free islands and NPC assembly remains unclear...
November 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29167340/hadv-protein-v-core-protein-is-targeted-by-the-host-sumoylation-machinery-to-limit-essential-viral-functions
#16
Nora Freudenberger, Tina Meyer, Peter Groitl, Thomas Dobner, Sabrina Schreiner
Human Adenoviruses (HAdV) are non-enveloped containing a linear, double-stranded DNA genome surrounded by an icosahedral capsid. To allow proper viral replication, the genome is imported through the nuclear-pore-complex associated with viral core proteins. Until now, the role of these incoming virion proteins during the early phase of infection was poorly understood.The core protein V is speculated to bridge core and the surrounding capsid. It binds the genome in a sequence-independent manner and localizes in the nucleus of infected cells, accumulating at nucleoli...
November 22, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29157868/selective-observation-of-charge-storing-ions-in-supercapacitor-electrode-materials
#17
Alexander C Forse, John M Griffin, Clare P Grey
Nuclear magnetic resonance (NMR) spectroscopy has emerged as a useful technique for probing the structure and dynamics of the electrode-electrolyte interface in supercapacitors, as ions inside the pores of the carbon electrodes can be studied separately from bulk electrolyte. However, in some cases spectral resolution can limit the information that can be obtained. In this study we address this issue by showing how cross polarisation (CP) NMR experiments can be used to selectively observe the in-pore ions in supercapacitor electrode materials...
November 4, 2017: Solid State Nuclear Magnetic Resonance
https://www.readbyqxmd.com/read/29155820/mass-spectrometry-based-quantification-of-the-cellular-response-to-ultraviolet-radiation-in-hela-cells
#18
Hong Xu, Xuanyi Chen, Nanjiao Ying, Meixia Wang, Xiaoli Xu, Rongyi Shi, Yuejin Hua
Ultraviolet (UV) irradiation is a common form of DNA damage that can cause pyrimidine dimers between DNA, which can cause gene mutations, even double-strand breaks and threaten genome stability. If DNA repair systems default their roles at this stage, the organism can be damaged and result in disease, especially cancer. To better understand the cellular response to this form of damage, we applied highly sensitive mass spectrometry to perform comparative proteomics of phosphorylation in HeLa cells. A total of 4367 phosphorylation sites in 2100 proteins were identified, many of which had not been reported previously...
2017: PloS One
https://www.readbyqxmd.com/read/29150488/membrane-binding-of-and-a-self-inhibitory-interaction-within-nup155-are-required-for-nuclear-pore-complex-formation
#19
Paola De Magistris, Marianna Tatarek-Nossol, Manfred Dewor, Wolfram Antonin
Nuclear pore complexes (NPCs) are the gateways through the nuclear envelope. How they form into a structure containing three rings and integrate into the nuclear envelope remains a challenging paradigm for coordinated assembly of macro-complexes. In vertebrates, the cytoplasmic and nucleoplasmic rings of NPCs are mostly formed by multiple copies of the Nup107-Nup160 complex, whereas the central, or inner ring is composed of Nup53, Nup93, Nup155 and the two paralogues Nup188 and Nup205. Inner ring assembly is only partially understood...
November 17, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/29142102/prolines-in-the-%C3%AE-helix-confer-the-structural-flexibility-and-functional-integrity-of-importin-%C3%AE
#20
Masahiro Kumeta, Hide A Konishi, Wanzhen Zhang, Sayuri Sakagami, Shige H Yoshimura
The karyopherin family of nuclear transport receptors is composed of a long array of amphiphilic α-helices and undergoes flexible conformational changes to pass through the hydrophobic crowding barrier of the nuclear pore. Here, we focused on the characteristic enrichment of prolines in the middle of the outer α-helices of importin β. When these prolines were substituted with alanine, nuclear transport activity was reduced drastically in vivo and in vitro, and caused a severe defect in mitotic progression...
November 15, 2017: Journal of Cell Science
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