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Nuclear lamin

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https://www.readbyqxmd.com/read/29773057/nucleophagy-plays-a-major-role-in-human-diseases
#1
Nian Fu, XueFeng Yang, Linxi Chen
Nucleophagy is a selective autophagy, which selectively remove damaged or non-essential nuclear material from a cell by the autophagy pathway. Additionally, nucleophagy is crucial for promoting cell longevity and ensure body proper function. Increasing evidences have shown that nucleophagy may play a major role in such human diseases as degenerative disorders, tumorigenesis, malnutrition and metabolic disorders, parakeratosis and psoriasis. Studies indicated that nucleophagy can improve degenerative disorders by delaying premature cell senescence, prevent malnutrition and metabolic disorder via maintaining nuclear structure and releasing nutrients for energy production, and alleviate parakeratosis and psoriasis...
May 17, 2018: Current Drug Targets
https://www.readbyqxmd.com/read/29772801/ogt-o-glcnac-transferase-selectively-modifies-multiple-residues-unique-to-lamin-a
#2
Dan N Simon, Amanda Wriston, Qiong Fan, Jeffrey Shabanowitz, Alyssa Florwick, Tejas Dharmaraj, Sherket B Peterson, Yosef Gruenbaum, Cathrine R Carlson, Line M Grønning-Wang, Donald F Hunt, Katherine L Wilson
The LMNA gene encodes lamins A and C with key roles in nuclear structure, signaling, gene regulation, and genome integrity. Mutations in LMNA cause over 12 diseases ('laminopathies'). Lamins A and C are identical for their first 566 residues. However, they form separate filaments in vivo, with apparently distinct roles. We report that lamin A is β- O -linked N -acetylglucosamine- (O -GlcNAc)-modified in human hepatoma (Huh7) cells and in mouse liver. In vitro assays with purified O -GlcNAc transferase (OGT) enzyme showed robust O -GlcNAcylation of recombinant mature lamin A tails (residues 385⁻646), with no detectable modification of lamin B1, lamin C, or 'progerin' (Δ50) tails...
May 17, 2018: Cells
https://www.readbyqxmd.com/read/29764566/laminopathies-mutations-on-single-gene-and-various-human-genetic-diseases
#3
So-Mi Kang, Min-Ho Yoon, Bum-Joon Park
Lamin A and its alternative splicing product Lamin C are the key intermediate filaments (IFs) of the inner nuclear membrane intermediate filament. Lamin A/C forms the inner nuclear mesh with Lamin B and works as a frame with a nuclear shape. In addition to supporting the function of nucleus, nuclear lamins perform important roles such as holding the nuclear pore complex and chromatin. However, mutations on the Lamin A or Lamin B related proteins induce various types of human genetic disorders and diseases including premature aging syndromes, muscular dystrophy, lipodystrophy and neuropathy...
May 16, 2018: BMB Reports
https://www.readbyqxmd.com/read/29760459/gata4-dependent-regulation-of-the-secretory-phenotype-via-mcp-1-underlies-lamin-a-mediated-human-mesenchymal-stem-cell-aging
#4
Jin Young Lee, Kyung-Rok Yu, Byung-Chul Lee, Insung Kang, Jae-Jun Kim, Eui-Jung Jung, Hyung-Sik Kim, Yoojin Seo, Soon Won Choi, Kyung-Sun Kang
Defects in the nuclear lamina occur during physiological aging and as. result of premature aging disorders. Aging is also accompanied by an increase in transcription of genes encoding cytokines and chemokines,. phenomenon known as the senescence-associated secretory phenotype (SASP). Progerin and prelamin. trigger premature senescence and loss of function of human mesenchymal stem cells (hMSCs), but little is known about how defects in nuclear lamin. regulate SASP. Here, we show that both progerin overexpression and ZMPSTE24 depletion induce paracrine senescence, especially through the expression of monocyte chemoattractant protein-1 (MCP-1), in hMSCs...
May 14, 2018: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29756146/effect-of-geometrical-constraints-on-human-pluripotent-stem-cell-nuclei-in-pluripotency-and-differentiation
#5
Eleonora Grespan, Giovanni G Giobbe, Florent Badique, Karine Anselme, Jürgen Rühe, Nicola Elvassore
Mechanical stimuli and geometrical constraints transmitted across the cytoskeleton to the nucleus affect the nuclear morphology and cell function. Human pluripotent stem cells (hPSCs) represent an effective tool for evaluating transitions in nuclear deformability from the pluripotent to differentiated stage, and for deciphering the underlying mechanisms. We report the first study that investigates the nuclear deformability induced by geometrical constraints of hPSCs both in the pluripotent stage and during early germ layer specification...
May 14, 2018: Integrative Biology: Quantitative Biosciences From Nano to Macro
https://www.readbyqxmd.com/read/29755599/nuclear-lamin-protein-c-is-linked-to-lineage-specific-whole-cell-mechanical-properties
#6
Rafael D González-Cruz, Jessica S Sadick, Vera C Fonseca, Eric M Darling
INTRODUCTION: Lamin proteins confer nuclear integrity and relay external mechanical cues that drive changes in gene expression. However, the influence these lamins have on whole-cell mechanical properties is unknown. We hypothesized that protein expression of lamins A, B1, and C would depend on the integrity of the actin cytoskeleton and correlate with cellular elasticity and viscoelasticity. METHODS: To test these hypotheses, we examined the protein expression of lamins A, B1, and C across five different cell lines with varied mechanical properties...
April 2018: Cellular and Molecular Bioengineering
https://www.readbyqxmd.com/read/29754147/non-senescent-hydra-tolerates-severe-disturbances-in-the-nuclear-lamina
#7
Alexander Klimovich, Arvid Rehm, Jörg Wittlieb, Eva-Maria Herbst, Ricardo Benavente, Thomas C G Bosch
The cnidarian Hydra is known for its unlimited lifespan and non-senescence, due to the indefinite self-renewal capacity of its stem cells. While proteins of the Lamin family are recognized as critical factors affecting senescence and longevity in human and mice, their putative role in the extreme longevity and non-senescence in long-living animals remains unknown. Here we analyze the role of a single lamin protein in non-senescence of Hydra . We demonstrate that proliferation of stem cells in Hydra is robust against the disturbance of Lamin expression and localization...
May 10, 2018: Aging
https://www.readbyqxmd.com/read/29753763/e3-ubiquitin-ligase-hecw2-targets-pcna-and-lamin-b1
#8
Vidhya Krishnamoorthy, Richa Khanna, Veena K Parnaik
Lamins constitute the major architectural proteins of the nuclear lamina that help in maintaining nuclear organization. Mutations in lamins are associated with diverse degenerative diseases, collectively termed laminopathies. HECW2, a HECT-type E3 ubiquitin ligase, is transcriptionally upregulated in HeLa cells expressing Emery-Dreifuss muscular dystrophy-causing-lamin A mutants. However, the role of HECW2 upregulation in mediating downstream effects in lamin mutant-expressing cells was previously unexplored...
May 10, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29750601/allelic-heterogeneity-of-lamin-a-c-phenotypes-and-molecular-mechanism-behind-it
#9
Jelena Perovanovic, Eric P Hoffman
Mutations in the LMNA gene cause a broad range of clinical syndromes that show tissue-restricted abnormalities of post mitotic tissues, such as muscle, nerve, heart, and adipose tissue. Mutations in other nuclear envelope proteins cause clinically overlapping disorders. The majority of mutations are dominant single amino acid changes (toxic protein produced by the single mutant gene), and patients are heterozygous with both normal and abnormal proteins. Experimental support has been provided for different models of cellular pathogenesis in nuclear envelope diseases, including changes in heterochromatin formation at the nuclear membrane (epigenomics), changes in the timing of steps during terminal differentiation of cells, and structural abnormalities of the nuclear membrane...
May 11, 2018: Physiological Genomics
https://www.readbyqxmd.com/read/29738692/an-inducible-damid-system-for-profiling-interactions-of-nuclear-lamina-protein-component-lamin-b1-with-chromosomes-in-mouse-cells
#10
E N Kozhevnikova, A E Leshchenko, A V Pindyurin
At the level of DNA organization into chromatin, there are mechanisms that define gene expression profiles in specialized cell types. Genes within chromatin regions that are located at the nuclear periphery are generally expressed at lower levels; however, the nature of this phenomenon remains unclear. These parts of chromatin interact with nuclear lamina proteins like Lamin B1 and, therefore, can be identified in a given cell type by chromatin profiling of these proteins. In this study, we created and tested a Dam Identification (DamID) system induced by Cre recombinase using Lamin B1 and mouse embryonic fibroblasts...
May 2018: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/29731750/macrophage-lamin-a-c-regulates-inflammation-and-the-development-of-obesity-induced-insulin-resistance
#11
Youngjo Kim, Princess Wendy Bayona, Miri Kim, Jiyeon Chang, Sunmin Hong, Yoona Park, Andrea Budiman, Yong-Jin Kim, Chang Yong Choi, Woo Seok Kim, Jongsoon Lee, Kae Won Cho
Obesity-induced chronic low-grade inflammation, in particular in adipose tissue, contributes to the development of insulin resistance and type 2 diabetes. However, the mechanism by which obesity induces adipose tissue inflammation has not been completely elucidated. Recent studies suggest that alteration of the nuclear lamina is associated with age-associated chronic inflammation in humans and fly. These findings led us to investigate whether the nuclear lamina regulates obesity-mediated chronic inflammation...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29722648/distinct-safe-zones-at-the-nuclear-envelope-ensure-robust-replication-of-heterochromatic-chromosome-regions
#12
Hani Ebrahimi, Hirohisa Masuda, Devanshi Jain, Julia Promisel Cooper
Chromosome replication and transcription occur within a complex nuclear milieu whose functional subdomains are beginning to be mapped out. Here we delineate distinct domains of the fission yeast nuclear envelope (NE), focusing on regions enriched for the inner NE protein, Bqt4, or the lamin interacting domain protein, Lem2. Bqt4 is relatively mobile around the NE and acts in two capacities. First, Bqt4 tethers chromosome termini and the mat locus to the NE specifically while these regions are replicating. This positioning is required for accurate heterochromatin replication...
May 3, 2018: ELife
https://www.readbyqxmd.com/read/29719066/displacing-squeezing-and-ramming-the-role-of-nuclear-lamins-in-leukocyte-migration
#13
EDITORIAL
Federica M Marelli-Berg, Suchita Nadkarni
No abstract text is available yet for this article.
May 2, 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29718780/isoprenoids-and-protein-prenylation-implications-in-the-pathogenesis-and-therapeutic-intervention-of-alzheimer-s-disease
#14
Angela Jeong, Kiall Francis Suazo, W Gibson Wood, Mark D Distefano, Ling Li
The mevalonate-isoprenoid-cholesterol biosynthesis pathway plays a key role in human health and disease. The importance of this pathway is underscored by the discovery that two major isoprenoids, farnesyl and geranylgeranyl pyrophosphate, are required to modify an array of proteins through a process known as protein prenylation, catalyzed by prenyltransferases. The lipophilic prenyl group facilitates the anchoring of proteins in cell membranes, mediating protein-protein interactions and signal transduction...
June 2018: Critical Reviews in Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/29717016/sun2-modulates-hiv-1-infection-and-latency-through-association-with-lamin-a-c-to-maintain-the-repressive-chromatin
#15
Wei-Wei Sun, Shi Jiao, Li Sun, Zhaocai Zhou, Xia Jin, Jian-Hua Wang
The postintegrational latency of HIV-1 is characterized by reversible silencing of long terminal repeat (LTR)-driven transcription of the HIV genome. It is known that the formation of repressive chromatin at the 5'-LTR of HIV-1 proviral DNA impedes viral transcription by blocking the recruitment of positive transcription factors. How the repressive chromatin is formed and modulated during HIV-1 infection remains elusive. Elucidation of which chromatin reassembly factor mediates the reorganization of chromatin is likely to facilitate the understanding of the host's modulation of HIV-1 transcription and latency...
May 1, 2018: MBio
https://www.readbyqxmd.com/read/29703891/targeting-of-nat10-enhances-healthspan-in-a-mouse-model-of-human-accelerated-aging-syndrome
#16
Gabriel Balmus, Delphine Larrieu, Ana C Barros, Casey Collins, Monica Abrudan, Mukerrem Demir, Nicola J Geisler, Christopher J Lelliott, Jacqueline K White, Natasha A Karp, James Atkinson, Andrea Kirton, Matt Jacobsen, Dean Clift, Raphael Rodriguez, David J Adams, Stephen P Jackson
Hutchinson-Gilford Progeria Syndrome (HGPS) is a rare, but devastating genetic disease characterized by segmental premature aging, with cardiovascular disease being the main cause of death. Cells from HGPS patients accumulate progerin, a permanently farnesylated, toxic form of Lamin A, disrupting the nuclear shape and chromatin organization, leading to DNA-damage accumulation and senescence. Therapeutic approaches targeting farnesylation or aiming to reduce progerin levels have provided only partial health improvements...
April 27, 2018: Nature Communications
https://www.readbyqxmd.com/read/29700484/computational-3d-genome-modeling-using-chrom3d
#17
Jonas Paulsen, Tharvesh Moideen Liyakat Ali, Philippe Collas
Chrom3D is a computational platform for 3D genome modeling that simulates the spatial positioning of chromosome domains relative to each other and relative to the nuclear periphery. In Chrom3D, chromosomes are modeled as chains of contiguous beads, in which each bead represents a genomic domain. In this protocol, a bead represents a topologically associated domain (TAD) mapped from ensemble Hi-C data. Chrom3D takes as input data significant pairwise TAD-TAD interactions determined from a Hi-C contact matrix, and TAD interactions with the nuclear periphery, determined by ChIP-sequencing of nuclear lamins to define lamina-associated domains (LADs)...
May 2018: Nature Protocols
https://www.readbyqxmd.com/read/29690642/autophagic-removal-of-farnesylated-carboxy-terminal-lamin-peptides
#18
Xiang Lu, Karima Djabali
The mammalian nuclear lamina proteins—prelamin A- and B-type lamins—are post-translationally modified by farnesylation, endoproteolysis, and carboxymethylation at a carboxy-terminal CAAX (C, cysteine; a, aliphatic amino acid; X, any amino acid) motif. However, prelamin A processing into mature lamin A is a unique process because it results in the production of farnesylated and carboxymethylated peptides. In cells from patients with Hutchinson⁻Gilford progeria syndrome, the mutant prelamin A protein, progerin, cannot release its prenylated carboxyl-terminal moiety and therefore remains permanently associated with the nuclear envelope (NE), causing severe nuclear alterations and a dysmorphic morphology...
April 23, 2018: Cells
https://www.readbyqxmd.com/read/29689196/transient-and-partial-nuclear-lamina-disruption-promotes-chromosome-movement-in-early-meiotic-prophase
#19
Jana Link, Dimitra Paouneskou, Maria Velkova, Anahita Daryabeigi, Triin Laos, Sara Labella, Consuelo Barroso, Sarai Pacheco Piñol, Alex Montoya, Holger Kramer, Alexander Woglar, Antoine Baudrimont, Sebastian Mathias Markert, Christian Stigloher, Enrique Martinez-Perez, Alexander Dammermann, Manfred Alsheimer, Monique Zetka, Verena Jantsch
Meiotic chromosome movement is important for the pairwise alignment of homologous chromosomes, which is required for correct chromosome segregation. Movement is driven by cytoplasmic forces, transmitted to chromosome ends by nuclear membrane-spanning proteins. In animal cells, lamins form a prominent scaffold at the nuclear periphery, yet the role lamins play in meiotic chromosome movement is unclear. We show that chromosome movement correlates with reduced lamin association with the nuclear rim, which requires lamin phosphorylation at sites analogous to those that open lamina network crosslinks in mitosis...
April 23, 2018: Developmental Cell
https://www.readbyqxmd.com/read/29684168/emerin-modulates-spatial-organization-of-chromosome-territories-in-cells-on-softer-matrices
#20
Roopali Pradhan, Devika Ranade, Kundan Sengupta
Cells perceive and relay external mechanical forces into the nucleus through the nuclear envelope. Here we examined the effect of lowering substrate stiffness as a paradigm to address the impact of altered mechanical forces on nuclear structure-function relationships. RNA sequencing of cells on softer matrices revealed significant transcriptional imbalances, predominantly in chromatin associated processes and transcriptional deregulation of human Chromosome 1. Furthermore, 3-Dimensional fluorescence in situ hybridization (3D-FISH) analyses showed a significant mislocalization of Chromosome 1 and 19 Territories (CT) into the nuclear interior, consistent with their transcriptional deregulation...
April 19, 2018: Nucleic Acids Research
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