A subclass of developmentally regulated lamins having a neutral isoelectric point. They are found to disassociate from nuclear membranes during mitosis.
A subclass of ubiquitously-expressed lamins having an acidic isoelectric point. They are found to remain bound to nuclear membranes during mitosis.
Nuclear matrix proteins that are structural components of the NUCLEAR LAMINA. They are found in most multicellular organisms.
A lattice of fibrils which covers the entire inner surface of the nuclear envelope and interlinks nuclear pores (NUCLEAR PORE).
The membrane system of the CELL NUCLEUS that surrounds the nucleoplasm. It consists of two concentric membranes separated by the perinuclear space. The structures of the envelope where it opens to the cytoplasm are called the nuclear pores (NUCLEAR PORE).
An abnormal congenital condition, associated with defects in the LAMIN TYPE A gene, which is characterized by premature aging in children, where all the changes of cell senescence occur. It is manifested by premature greying; hair loss; hearing loss (DEAFNESS); cataracts (CATARACT); ARTHRITIS; OSTEOPOROSIS; DIABETES MELLITUS; atrophy of subcutaneous fat; skeletal hypoplasia; elevated urinary HYALURONIC ACID; and accelerated ATHEROSCLEROSIS. Many affected individuals develop malignant tumors, especially SARCOMA.
Two closely related polypeptides (molecular weight 7,000) isolated from the thymus gland. These hormones induce the differentiation of prothymocytes to thymocytes within the thymus. They also cause a delayed impairment of neuromuscular transmission in vivo and are therefore believed to be the agent responsible for myasthenia gravis.
A heterogenous group of inherited muscular dystrophy without the involvement of nervous system. The disease is characterized by MUSCULAR ATROPHY; MUSCLE WEAKNESS; CONTRACTURE of the elbows; ACHILLES TENDON; and posterior cervical muscles; with or without cardiac features. There are several INHERITANCE PATTERNS including X-linked (X CHROMOSOME), autosomal dominant, and autosomal recessive gene mutations.
Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.
Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)
A collection of heterogenous conditions resulting from defective LIPID METABOLISM and characterized by ADIPOSE TISSUE atrophy. Often there is redistribution of body fat resulting in peripheral fat wasting and central adiposity. They include generalized, localized, congenital, and acquired lipodystrophy.
Inherited conditions characterized by the partial loss of ADIPOSE TISSUE, either confined to the extremities with normal or increased fat deposits on the face, neck and trunk (type 1), or confined to the loss of SUBCUTANEOUS FAT from the limbs and trunk (type 2). Type 3 is associated with mutation in the gene encoding PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR GAMMA.
Changes in the organism associated with senescence, occurring at an accelerated rate.
The residual framework structure of the CELL NUCLEUS that maintains many of the overall architectural features of the cell nucleus including the nuclear lamina with NUCLEAR PORE complex structures, residual CELL NUCLEOLI and an extensive fibrogranular structure in the nuclear interior. (Advan. Enzyme Regul. 2002; 42:39-52)
A post-translational modification of proteins by the attachment of an isoprenoid to the C-terminal cysteine residue. The isoprenoids used, farnesyl diphosphate or geranylgeranyl diphosphate, are derived from the same biochemical pathway that produces cholesterol.
A short pro-domain caspase that plays an effector role in APOPTOSIS. It is activated by INITIATOR CASPASES such as CASPASE 7; CASPASE 8; and CASPASE 10. Isoforms of this protein exist due to multiple alternative splicing of its MESSENGER RNA.
The quality of surface form or outline of the CELL NUCLEUS.
Abnormally infrequent menstruation.
One of the Indian Ocean Islands, east of Madagascar. Its capital is Saint-Denis. It was discovered in 1507 by the Portuguese and claimed by France in 1638. It was first colonized in 1662 as Isle de Bourbon but renamed Reunion in 1793. In 1946 it was made an overseas department of France. The name commemorates the reunion of the revolutionaries from Marseilles with the National Guard in Paris in 1792. (From Webster's New Geographical Dictionary, 1988, p1011; Room, Brewer's Dictionary of Names, 1992, p454; French Embassy)
A synthetic progestational hormone used alone or in combination with estrogens as an oral contraceptive.
Development of SEXUAL MATURATION in boys and girls at a chronological age that is 2.5 standard deviations below the mean age at onset of PUBERTY in the population. This early maturation of the hypothalamic-pituitary-gonadal axis results in sexual precocity, elevated serum levels of GONADOTROPINS and GONADAL STEROID HORMONES such as ESTRADIOL and TESTOSTERONE.
A condition observed in WOMEN and CHILDREN when there is excess coarse body hair of an adult male distribution pattern, such as facial and chest areas. It is the result of elevated ANDROGENS from the OVARIES, the ADRENAL GLANDS, or exogenous sources. The concept does not include HYPERTRICHOSIS, which is an androgen-independent excessive hair growth.
A stage of development at which the ADRENAL GLANDS undergo maturation leading to the capability of producing increasing amounts of adrenal androgens, DEHYDROEPIANDROSTERONE and ANDROSTENEDIONE. Adrenarche usually begins at about 7 or 8 years of age before the signs of PUBERTY and continues throughout puberty.
A filament-like structure consisting of a shaft which projects to the surface of the SKIN from a root which is softer than the shaft and lodges in the cavity of a HAIR FOLLICLE. It is found on most surfaces of the body.
A terminal section of a chromosome which has a specialized structure and which is involved in chromosomal replication and stability. Its length is believed to be a few hundred base pairs.
A ubiquitously expressed telomere-binding protein that is present at TELOMERES throughout the cell cycle. It is a suppressor of telomere elongation and may be involved in stabilization of telomere length. It is structurally different from TELOMERIC REPEAT BINDING PROTEIN 1 in that it contains basic N-terminal amino acid residues.
Therapeutic closure of spaces caused by the extraction of teeth, the congenital absence of teeth, or the excessive space between teeth.
A ubiquitously expressed telomere-binding protein that is present at TELOMERES throughout the CELL CYCLE. It is a suppressor of telomere elongation and may be involved in stabilization of telomere length. It is structurally different from TELOMERIC REPEAT BINDING PROTEIN 2 in that it contains acidic N-terminal amino acid residues.
The process by which cells convert mechanical stimuli into a chemical response. It can occur in both cells specialized for sensing mechanical cues such as MECHANORECEPTORS, and in parenchymal cells whose primary function is not mechanosensory.
Proteins that are coded by immediate-early genes, in the absence of de novo protein synthesis. The term was originally used exclusively for viral regulatory proteins that were synthesized just after viral integration into the host cell. It is also used to describe cellular proteins which are synthesized immediately after the resting cell is stimulated by extracellular signals.
A large group of proteins that control APOPTOSIS. This family of proteins includes many ONCOGENE PROTEINS as well as a wide variety of classes of INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS such as CASPASES.
Organic or inorganic compounds that contain the -N3 group.
Antibodies produced by a single clone of cells.
A genus in the family ORTHOMYXOVIRIDAE causing influenza and other diseases in humans and animals. It contains many strains as well as antigenic subtypes of the integral membrane proteins hemagglutinin (HEMAGGLUTININS) and NEURAMINIDASE. The type species is INFLUENZA A VIRUS.
A cytochrome oxidase inhibitor which is a nitridizing agent and an inhibitor of terminal oxidation. (From Merck Index, 12th ed)
Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the ANTIGEN (or a very similar shape) that induced their synthesis in cells of the lymphoid series (especially PLASMA CELLS).
Sound that expresses emotion through rhythm, melody, and harmony.
Professional nurses who have received postgraduate training in midwifery.
The use of music as an adjunctive therapy in the treatment of neurological, mental, or behavioral disorders.
The upper part of the human body, or the front or upper part of the body of an animal, typically separated from the rest of the body by a neck, and containing the brain, mouth, and sense organs.
Works containing information articles on subjects in every field of knowledge, usually arranged in alphabetical order, or a similar work limited to a special field or subject. (From The ALA Glossary of Library and Information Science, 1983)
An opening through the NUCLEAR ENVELOPE formed by the nuclear pore complex which transports nuclear proteins or RNA into or out of the CELL NUCLEUS and which, under some conditions, acts as an ion channel.

Subcellular localization and partial purification of prelamin A endoprotease: an enzyme which catalyzes the conversion of farnesylated prelamin A to mature lamin A. (1/572)

The nuclear lamina protein, lamin A is produced by proteolytic cleavage of a 74 kDa precursor protein, prelamin A. The conversion of this precursor to mature lamin A is mediated by a specific endoprotease, prelamin A endoprotease. Subnuclear fractionation indicates that the prelamin A endoprotease is localized at the nuclear membrane. The enzyme appears to be an integral membrane protein, as it can only be removed from the nuclear envelope with detergent. It is effectively solubilized by the detergent n-octyl-beta-D-glucopyranoside and can be partially-purified (approximately 1200-fold) by size exclusion and cation exchange (Mono S) chromatography. Prelamin A endoprotease from HeLa cells was eluted from Mono S with 0.3 M sodium chloride as a single peak of activity. SDS-PAGE analysis of this prelamin A endoprotease preparation shows that it contains one major polypeptide at 65 kDa and smaller amounts of a second 68 kDa polypeptide. Inhibition of the enzyme activity in this preparation by specific serine protease inhibitors is consistent with the enzyme being a serine protease.  (+info)

Heart to heart: from nuclear proteins to Emery-Dreifuss muscular dystrophy. (2/572)

Emery-Dreifuss muscular dystrophy has some remarkably specific features, with only cardiac and skeletal tissues being affected. Equally remarkably, the disease is caused by mutations in widely expressed genes for the nuclear membrane/lamina proteins, emerin and lamin A/C. How do mutations in proteins at the heart of the cell lead to stiff joints and sudden heart failure? This and related questions are the subject of this review.  (+info)

Dynamics of the nuclear lamina as monitored by GFP-tagged A-type lamins. (3/572)

The behavior of chimeric proteins consisting of A-type lamins and green fluorescent protein (GFP) was studied to investigate the localization and dynamics of nuclear lamins in living cells. Cell line CHO-K1 was transfected with cDNA constructs encoding fusion proteins of lamin A-GFP, lamin Adelta10-GFP, or lamin C-GFP. In the interphase nucleus lamin-GFP fluorescence showed a perinuclear localization and incorporation into the lamina for all three constructs. Our findings show for the first time that the newly discovered lamin A 10 protein is localized to the nuclear membrane. The GFP-tagged lamins were processed and behaved similarly to the endogenous lamin molecules, at least in cells that expressed physiological levels of the GFP-lamins. In addition to the typical perinuclear localization, in the majority of transfected cells each individual A-type lamin-GFP revealed an extensive collection of branching intra- and trans-nuclear tubular structures, which showed a clear preference for a vertical orientation. Time-lapse studies of 3-D reconstructed interphase cells showed a remarkable stability in both number and location of these structures over time, while the lamina showed considerable dynamic movements, consisting of folding and indentation of large parts of the lamina. Fluorescence recovery after bleaching studies revealed a low protein turnover of both tubular and lamina-associated lamins. Repetitive bleaching of intranuclear areas revealed the presence of an insoluble intranuclear fraction of A-type lamins. Time-lapse studies of mitotic cells showed that reformation of the lamina and the tubular structures consisting of A-type lamins did not occur until after cytokinesis was completed.  (+info)

Decreased and aberrant nuclear lamin expression in gastrointestinal tract neoplasms. (4/572)

BACKGROUND: Altered expression of lamins A/C and B1, constituent proteins of the nuclear lamina, may occur during differentiation and has also been reported in primary lung cancer. AIMS: To examine the expression of these proteins in gastrointestinal neoplasms. PATIENTS: Archival human paraffin wax blocks and frozen tissue from patients undergoing surgical resection or endoscopic biopsy. METHODS: Immunohistochemistry and western blotting using polyclonal antisera against A type lamins and lamin B1. RESULTS: The expression of lamin A/C was reduced and was frequently undetectable by immunohistochemistry in all primary colon carcinomas and adenomas, and in 7/8 primary gastric cancers. Lamin B1 expression was reduced in all colon cancers, 16/18 colonic adenomas, and 6/8 gastric cancers. Aberrant, cytoplasmic labelling with both antibodies occurred in some colonic cancers and around one third of colonic adenomas. Cytoplasmic lamin A/C expression was detected in 3/8 gastric cancers. Lamin expression was reduced in gastric dysplasia, but not intestinal metaplasia, atrophy, or chronic gastritis. Lamin expression was low in carcinomas of oesophagus, prostate, breast, and uterus, but not pancreas. CONCLUSIONS: Reduced expression of nuclear lamins, sometimes together with aberrant, cytoplasmic immunoreactivity is common in gastrointestinal neoplasms. Altered lamin expression may be a biomarker of malignancy in the gastrointestinal tract.  (+info)

Colocalization of intranuclear lamin foci with RNA splicing factors. (5/572)

The lamins form a fibrous network underlying the inner nuclear membrane termed the nuclear lamina. In order to gain insights into the role of lamins in nuclear organization, we have characterized a monoclonal antibody (LA-2H10) raised against recombinant rat lamin A that labels nuclei in a speckled pattern in all cells of unsynchronized populations of HeLa and rat F-111 fibroblast cells, unlike the typical nuclear periphery staining by another monoclonal antibody to lamin A, LA-2B3. In immunolocalization studies the lamin A speckles or foci were found to colocalize with the RNA splicing factors SC-35 and U5-116 kD, but not with p80 coilin found in coiled bodies. Lamin B1 was also associated with these foci. These foci dispersed when cells entered mitosis and reformed during anaphase. The differential reactivity of LA-2H10 and LA-2B3 was retained after nuclei were extracted with detergents, nucleases and salt to disrupt interactions of lamins with chromatin and other nuclear proteins. Using deletion fragments of recombinant lamin A, the epitope recognized by LA-2H10 was located between amino acids 171 and 246. Our findings are consistent with a structural role for lamins in supporting nuclear compartments containing proteins involved in RNA splicing.  (+info)

Missense mutations in the rod domain of the lamin A/C gene as causes of dilated cardiomyopathy and conduction-system disease. (6/572)

BACKGROUND: Inherited mutations cause approximately 35 percent of cases of dilated cardiomyopathy; however, few genes associated with this disease have been identified. Previously, we located a gene defect that was responsible for autosomal dominant dilated cardiomyopathy and conduction-system disease on chromosome 1p1-q21, where nuclear-envelope proteins lamin A and lamin C are encoded by the LMNA (lamin A/C) gene. Mutations in the head or tail domain of this gene cause Emery-Dreifuss muscular dystrophy, a childhood-onset disease characterized by joint contractures and in some cases by abnormalities of cardiac conduction during adulthood. METHODS: We evaluated 11 families with autosomal dominant dilated cardiomyopathy and conduction-system disease. Sequences of the lamin A/C exons were determined in probands from each family, and variants were confirmed by restriction-enzyme digestion. The genotypes of the family members were ascertained. RESULTS: Five novel missense mutations were identified: four in the alpha-helical-rod domain of the lamin A/C gene, and one in the lamin C tail domain. Each mutation caused heritable, progressive conduction-system disease (sinus bradycardia, atrioventricular conduction block, or atrial arrhythmias) and dilated cardiomyopathy. Heart failure and sudden death occurred frequently within these families. No family members with mutations had either joint contractures or skeletal myopathy. Serum creatine kinase levels were normal in family members with mutations of the lamin rod but mildly elevated in some family members with a defect in the tail domain of lamin C. CONCLUSIONS: Genetic defects in distinct domains of the nuclear-envelope proteins lamin A and lamin C selectively cause dilated cardiomyopathy with conduction-system disease or autosomal dominant Emery-Dreifuss muscular dystrophy. Missense mutations in the rod domain of the lamin A/C gene provide a genetic cause for dilated cardiomyopathy and indicate that this intermediate filament protein has an important role in cardiac conduction and contractility.  (+info)

Lamin A/C gene mutation associated with dilated cardiomyopathy with variable skeletal muscle involvement. (7/572)

BACKGROUND: Dilated cardiomyopathy is a form of heart muscle disease characterized by impaired systolic function and ventricular dilation. Familial transmission of the disease is frequently observed, and genetic heterogeneity is indicated by clinical and morphological variability in the disease phenotype. In the family MDDC1 reported here, the disease phenotype is severe and characterized by an autosomal dominant pattern of transmission. In addition, the majority of affected family members show signs of mild skeletal muscle involvement. METHODS AND RESULTS: On the basis of the clinical observation of both cardiac and skeletal muscle abnormalities in the MDDC1 family, the lamin A/C gene was examined in this kindred. Coding regions were polymerase chain reaction-amplified from genomic DNA and sequenced. A single nucleotide deletion was identified within exon 6, and all affected individuals were found to be heterozygous for this deletion. CONCLUSIONS: Heterozygosity for a single nucleotide deletion in exon 6 of lamin A/C segregates with both the cardiac and skeletal abnormalities observed in the MDDC1 family.  (+info)

DNase I hypersensitive sites and transcriptional activation of the lamin A/C gene. (8/572)

The lamin A/C gene encodes subtypes of nuclear lamins, which are involved in nuclear envelope formation, and was recently identified as the responsible gene for the autosomal dominant Emery-Dreifuss muscular dystrophy. Expression of the lamin A/C gene is developmentally regulated but little is known about the regulatory mechanism. Previous studies of lamin A/C expression suggested that the chromatin structure is important for the regulation of its expression. To elucidate the regulatory mechanism of the lamin A/C gene expression, we have analysed the functional region of the mouse lamin A/C promoter and the chromatin structure of the gene in terms of nucleosome structure and DNase I hypersensitivity. Our analyses revealed disruption of the nucleosome array at the promoter region and the presence of multiple DNase I hypersensitive sites (HSs) which were specifically associated with expression of the lamin A/C gene. Inclusion of a segment which contained the HSs in a lamin A/C promoter-luciferase reporter plasmid showed no effect on the transfected promoter activity in transient expression assays. On the other hand, substantial enhancement of the promoter activity was detected when the transfected DNA was stably integrated into the genome, suggesting the importance of the HSs in the regulation of lamin A/C expression.  (+info)

We investigated emerin localisation in two different human cell lines that were deficient for synthesis of lamins A and C and two further cell lines that were deficient for lamin A synthesis and in which lamin C was mis-localised to the nucleolus. In each cell line either all or a majority of emerin was mis-localised to the ER. In addition, we used a dominant negative mutant of lamin B1 that selectively eliminates lamins A and C but not lamins B1 and B2 from the NE of HeLa cells. A consequence of eliminating lamins A and C from the NE was that emerin relocated from the NE to the ER, where it formed insoluble inclusions.. Our data suggest that lamin A has a central role in tethering both emerin and lamin C to the NE. The following evidence supports this model. Association of lamin C with the NE in two of the cell lines reported here is dependent upon the presence of lamin A, and in its absence lamin C organisation is disrupted such that most (SW 13) or all (Ramos) is mis-localised to the ...
Five (26%) LMNA mutation carriers with an enlarged and dysfunctional left ventricle were older (67 ± 8 vs. 39 ± 14 years) and had a higher pro-B-type natriuretic peptide level (median 333 ng/l [25th to 75th percentiles: 62 to 1,943] vs. median 66 ng/l [25th to 75th percentiles: 29 to 107]) than LMNA mutation carriers with normal LV dimension and function (both p , 0.05). In all LMNA mutation carriers, PRA and catecholamine levels were within normal range, whereas the plasma aldosterone level was close to the upper normal limit (median 140 pg/ml [25th to 75th percentiles: 75 to 170], reference values: 20 to 180 pg/ml). Eight LMNA mutation carriers (42%) showed myocardial LGE with a patchy (n = 3) or mid wall (n = 5) pattern. In LMNA mutation carriers, LGE was more frequently detected in carriers with LV dysfunction (4 of 5 patients, 80%) compared with those with normal LV dimension and function (4 of 14 [29%], p , 0.05). Myocardial LGE was more common in carriers with first-degree ...
TY - JOUR. T1 - The LMNA mutation p.Arg321Ter associated with dilated cardiomyopathy leads to reduced expression and a skewed ratio of lamin A and lamin C proteins. AU - Al-Saaidi, Rasha. AU - Rasmussen, Torsten Bloch. AU - Palmfeldt, Johan. AU - Nissen, Peter H. AU - Beqqali, Abdelaziz. AU - Hansen, Jakob. AU - Pinto, Yigal M. AU - Boesen, Thomas. AU - Bross, Peter. AU - Mogensen, Jens. N1 - ; LMNA; Laminopathies; Premature termination codon mutation; Nonsense mediated mRNA decay; Haploinsufficiency PY - 2013/8/31. Y1 - 2013/8/31. N2 - Dilated cardiomyopathy (DCM) is a disease of the heart muscle characterized by cardiac chamber enlargement and reduced systolic function of the left ventricle. Mutations in the LMNA gene represent the most frequent known genetic cause of DCM associated with disease of the conduction systems. The LMNA gene generates two major transcripts encoding the nuclear lamina major components lamin A and lamin C by alternative splicing. Both haploinsuffiency and dominant ...
Author: Riemer, D. et al.; Genre: Journal Article; Published in Print: 1994-04; Keywords: DROSOPHILA; EVOLUTION; GENE ORGANIZATION; INTERMEDIATE; FILAMENTS; LAMINS|br/|; Title: The organization of the gene for Drosophila lamin C: limited homology with vertebrate lamin genes and lack of homology versus the Drosophila lamin Dmo gene.
The nucleoskeletal protein lamina-associated polypeptide 2(α) (LAP2*) contains a large, unique C terminus and differs significantly from its alternatively spliced, mostly membrane-integrated isoforms, such as LAP2beta. Unlike lamin B-binding LAP2beta, LAP2alpha was found by confocal immunofluorescence microscopy to colocalize preferentially with A-type lamins in the newly formed nuclei assembled after mitosis. While only a subfraction of lamins A and C (lamin A/C) was associated with the predominantly nuclear LAP2alpha in telophase, the majority of lamin A/C colocalized with LAP2alpha in G(1)-phase nuclei. Furthermore, selective disruption of A-type lamin structures by overexpression of lamin mutants in HeLa cells caused a redistribution of LAP2alpha. Coimmunoprecipitation experiments revealed that a fraction of lamin A/C formed a stable, SDS-resistant complex with LAP2alpha in interphase cells and in postmetaphase cell extracts. Blot overlay binding studies revealed a direct binding of ...
RATIONALE: Mutations in the LMNA gene, which encodes the nuclear lamina proteins lamin A and lamin C, are the most common cause of familial dilated cardiomyopathy (DCM). Mechanical stress-induced apoptosis has been proposed as the mechanism underpinning DCM in lamin A/C-deficient hearts, but supporting in vivo evidence has been lacking. OBJECTIVE: Our aim was to study interventions to modify mechanical stress in heterozygous Lmna knockout (Lmna(+/-)) mice. METHODS AND RESULTS: Cardiac structure and function were evaluated before and after exercise training, thoracic aortic constriction, and carvedilol treatment. Lmna(+/-) mice develop adult-onset DCM with relatively more severe disease in males. Lmna(+/-) cardiomyocytes show altered nuclear morphology and perinuclear desmin organization, with enhanced responses to hypo-osmotic stress indicative of cytoskeletal instability. Despite these structural defects that provide a template for mechanical stress-induced damage, young Lmna(+/-) mice ...
LMNA-related disorders are caused by mutations in the LMNA gene, which encodes for the nuclear envelope proteins, lamin A and C, via alternative splicing. Laminopathies are associated with a wide range of disease phenotypes, including neuromuscular, cardiac, metabolic disorders and premature aging syndromes. The most frequent diseases associated with mutations in the LMNA gene are characterized by skeletal and cardiac muscle involvement. This review will focus on genetics and clinical features of laminopathies affecting primarily skeletal muscle. Although only symptomatic treatment is available for these patients, many achievements have been made in clarifying the pathogenesis and improving the management of these diseases.
The cell nucleus is structurally and functionally organized by lamins, intermediate filament proteins that form the nuclear lamina. Point mutations in genes that encode a specific subset of lamins, the A-type lamins, cause a spectrum of diseases termed laminopathies. Recent evidence points to a role for A-type lamins in intracellular redox homeostasis. To determine whether lamin A/C depletion and prelamin A accumulation differentially induce oxidative stress, we have performed a quantitative microscopy-based analysis of reactive oxygen species (ROS) levels and mitochondrial membrane potential (Deltapsim) in human fibroblasts subjected to sustained siRNA-mediated knockdown of LMNA and ZMPSTE24, respectively. We measured a highly significant increase in basal ROS levels and an even more prominent rise of induced ROS levels in lamin A/C depleted cells, eventually resulting in Deltapsim hyperpolarization and apoptosis. Depletion of ZMPSTE24 on the other hand, triggered a senescence pathway that was ...
Laminopathies Meetings at the Kings College Bush House in London! The 9th UK Nuclear Envelope Meeting -3rd International Meeting on Laminopathies Joint Conference will take place in London on September 2-5 2019. A Satellite Meeting of the European Network for Laminopathies will take place on September 3-5.
Lamin A and lamin C, both products of Lmna, are key components of the nuclear lamina. In the mouse, a deficiency in both lamin A and lamin C leads to slow growth, muscle weakness, and death by 6 weeks of age. Fibroblasts deficient in lamins A and C contain misshapen and structurally weakened nuclei, …
24/4/2010. Năm nay, Trường về Khoa học máy tính (SCS) của Carnegie Mellon được xếp hạng thứ nhất trong cả nước giữa tất cả các chương trình khoa học máy tính trong ấn bản 2011 của tạp chí News & World Report về Trường tốt nhất nước Mĩ. Năm ngoái, 2009, Trường về Khoa học máy tính của Carnegie Mellon được xếp hạng thứ tư trong cả nước. Trong các phân loại chuyên môn hơn, SCS xếp hạng thứ nhất về ngôn ngữ lập trình, xếp hạng hai về trí tuệ nhân tạo, xếp hạng ba về hệ thông tin và hạng năm về lí thuyết tính toán.. Carnegie Mellon nỗ lực thúc đẩy biên giới của nghiên cứu và giáo dục trong khoa học máy tính, Dean Randal E. Bryant của SCS nói. Chúng tôi theo đuổi một chương trình nghị sự rất rộng, trải theo cả lí thuyết và thiết kế máy tính, cũng như cách công nghệ thông tin có thể ...
Laminopathies are a group of rare genetic disorders caused by mutations in genes encoding proteins of the nuclear lamina. They are included in the more generic term nuclear envelopathies that was coined in 2000 for diseases associated with defects of the nuclear envelope.[2] Since the first reports of laminopathies in the late 1990s, increased research efforts have started to uncover the vital role of nuclear envelope proteins in cell and tissue integrity in animals.
Introduction: Mutations in the LMNA gene, encoding Lamin A/C, cause several distinct phenotypes collectively referred to as laminopathies. Cardiac involvement is the primary cause of death and manifests as dilated cardiomyopathy (DCM), conduction defects, arrhythmias, and sudden cardiac death. The pathogenesis of cardiac phenotype in laminopathies remains largely unknown.. Hypothesis: We posit that early pre-clinical RNA-Sequencing could identify the primary events in the heart in laminopathies.. Methods: Lmna-/- and control wild type (WT) mice were characterized for cardiac function (echocardiography) and cardiac histology at 2 and 4 weeks. Transcriptome was analyzed by RNA-Seq at 2 weeks, prior to expression of cardiac dysfunction, apoptosis, and fibrosis.. Results: Hierarchal clustering of 908 differentially expressed transcripts in the heart (q,0.05) showed distinct separation of the Lmna-/- and WT mice. Hypergeometric distribution of the enriched transcription factors (TFs) identified FOXO4 ...
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As of March 2016, we compared 17.37 Mb of Sanger DNA sequence generated at PreventionGenetics to NextGen sequence generated in other labs. We detected only 4 errors in our Sanger sequences, and these were all due to allele dropout during PCR. For Proficiency Testing, both external and internal, in the 12 years of our lab operation we have Sanger sequenced roughly 8,800 PCR amplicons. Only one error has been identified, and this was due to sequence analysis error.. Our Sanger sequencing is capable of detecting virtually all nucleotide substitutions within the PCR amplicons. Similarly, we detect essentially all heterozygous or homozygous deletions within the amplicons. Homozygous deletions which overlap one or more PCR primer annealing sites are detectable as PCR failure. Heterozygous deletions which overlap one or more PCR primer annealing sites are usually not detected (see Analytical Limitations). All heterozygous insertions within the amplicons up to about 100 nucleotides in length appear to ...
A Bugs Life (1998) BDRip 1080p H264 AAC-IceBane (Kingdom Release) A Bugs Life (1998) BDRip 1080p H264 AAC-IceBane (Kingdom Release) http://i32.fastpic.ru/big/2012/0206/73/cf6b43b8d2378333e3b8643d27bce173.jpg A Bugs Life (1998) BDRip 1080p H264 AAC-IceBane (Kingdom Release) Language: English 01:34:53 | 1920x816 | H264 - 4196Kbps | 23.976fps | AAC - 320Kbps | 2.99GB Genre: Animation | Adventure | Comedy IMDB Rating: 7.2/10 Every year, a bunch of grasshoppers come to the anthill and eat what
Rabbit polyclonal Lamin A + Lamin C (phospho S392) antibody. Validated in WB, ELISA, IHC, ICC/IF and tested in Mouse, Rat, Human. Cited in 5 publication(s). Independently reviewed in 1 review(s)…
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CHO-Anti-Human CD4 MAb (P/H) stable cell line is clonally-derived from a CHO cell line, which has been transfected with an anti-human CD4 MAb (P/H) gene to allow expression of the MAb. It is an example of a cell line transfected using our proprietary CBTGS gene screening and amplification system.
CoreLite X is the stiffest, lightest and most durable sandwich layer polyethylene construction on the market and noticeably enhances the Delphins progressive hull design, producing unprecedented dexterity for a plastic sea kayak and making you feel instantly more adept on the water.. In both appearance and performance, the P&H Delphin is entirely unique; over 45 years of Pyranha whitewater kayak innovation, infused with P&Hs design heritage that dates back to 1968 has produced a sea kayak that river paddlers looking to expand their horizons will feel instantly at home in, and that allows experienced seafarers to rediscover and build upon the same excitement felt when they first took to the waves.. The Delphins cockpit has been positioned further back than in traditional sea kayak design, giving a fine balance that, in combination with the progressive bow rocker, leaves the front of the boat just kissing the water, resulting in superb manoeuvrability and excellent positioning when riding even ...
Since the first description of matrix metalloproteinase (MMP)-1 as an interstitial collagenase, great importance has been ascribed to this enzyme in extracellular matrix remodeling during tumoral, inflammatory, and angiogenic processes. As more evidence for the role of MMPs in targeting nonmatrix substrates emerges, casual observations that intracellular MMP-1 is found in vitro and in vivo prompt investigation of the role that MMP-1 may play on basic cell functions such as cell division and apoptosis. Here we show for the first time that MMP-1 not only has extracellular functions but that it is strongly associated with mitochondria and nuclei and accumulates within the cells during the mitotlc phase of the cell cycle. On induction of apoptosis, MMP-1 co-localized with aggregated mitochondria and accumulated around fragmented nuclei. Inhibition of this enzyme by RNA interference or treatment with a broad MMP inhibitor caused faster degradation of lamin A, activation of caspases, and fragmentation ...
Progeria pictures, facts, symptoms, treatment, causes. Progeria disease is a genetic disorder characterized by rapid aging in children
Saunders, P H. and Very, D L., Serological response of a c57bl/6 congenic mutant to the c57bl lymphoma el4: detection and characterization of tumor- -associated antigens on el4. Abstr. (1982). Subject Strain Bibliography 1982. 2048 ...
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HÓA CHẤT. Cung cấp Hóa Chất Công nghiệp, nông nghiệp, thực phẩm, Chemical, Việt Nam,tinh Mùi, Hương Bột Màu
HÓA CHẤT. Cung cấp Hóa Chất Công nghiệp, nông nghiệp, thực phẩm, Chemical, Việt Nam,tinh Mùi, Hương Bột Màu
Progeria is a genetic disorder that results in the appearance of premature aging. Genetically, progeria is characterized by a mutation in lamin A, which results in misshapen cell nuclei and DNA damage. Remodelin is a 2-thiazolylhydrazone derivative that, at 10 µM, improves nuclear architecture, chromatin organization,
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Progeria is the progressive and extremely rare genetic disorder which causes a child to age rapidly, beginning in the first 2 years of life. This is the forum for discussing anything related to this health condition
Correcting the mutation that causes progeria with base editing leads to strong symptom reduction and longer lifespan in an animal model
Bar-Ilan Universitys Yuval Garini has pinpointed how the protein Lamin A ensures the stability of cell nulclei and genetic coding.
The KOMP Repository is located at the University of California Davis and Childrens Hospital Oakland Research Institute. Question? Comments? For Mice, Cells, and germplasm please contact us at [email protected], US 1-888-KOMP-MICE or International +1-530-752-KOMP, or for vectors [email protected] or +1-510-450-7917 ...
Vše, co chcete od dvířek: design, funkčnost, odolnost. Brilantní lesk, hluboký mat. Syrové dřevo, dokonalá imitace i kouzla moderních nanotechnologií.
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An assay system useful for the determination of NAD(P)H, NAD(P), or a substrate of an enzyme which reacts with the formation or comsumption of NAD(P)H. Concentrations of organic substrates for example
När farfar Trygve utövade frisksport var fritt handstående och handgång viktiga inslag i frisksportkulturen. Handstående kan tillämpas på de flesta na...
If you and fill-in DJ Lamin could do shows on the same day it would be a great showcase of electronic sounds. Great show, wish it was 3 hours long ...
oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, NAD(P)H as one donor, and incorporation of one atom of ...
|div| |p class=padding-top-2| |/p| |h3 class=product_top_heading|Restore Gut Health|/h3| |p class=product_details| |p class=product_details|Harmful intestinal invaders can wreak havoc on your health and keep you feeling sluggish, bloated,
Emery-Dreifuss muscular dystrophy (EDMD) is characterized by early contractures of elbows and Achilles tendons, slowly progressive muscle wasting and weakness, and a cardiomyopathy with conduction blocks which is life-threatening. Two modes of inheritance exist, X-linked (OMIM 310300) and autosomal …
Hutchinson-Gilford progeria syndrome (HGPS) is a rare human genetic disease that leads to a severe premature ageing phenotype, caused by mutations in the LMNA gene. The LMNA gene codes for lamin-A and lamin-C proteins, which are structural components of the nuclear lamina. HGPS is usually caused by a de novo C1824T mutation that leads to the accumulation of a dominant negative form of lamin-A called progerin. Progerin also accumulates physiologically in normal ageing cells as a rare splicing form of lamin-A transcripts. From this perspective, HGPS cells seem to be good candidates for the study of the physiological mechanisms of ageing. Progerin accumulation leads to faster cellular senescence, stem cell depletion and the progeroid phenotype. Tissues of mesodermic origin are especially affected by HGPS. HGPS patients usually have a bad quality of life and, with current treatments, their life expectancy does not exceed their second decade at best. Though progerin can be expressed in almost any tissue,
Hutchinson-Gilford progeria syndrome (HGPS) is an extremely rare genetic disorder wherein symptoms resembling aspects of aging are manifested at a very early age. It is a genetic condition that occurs due to a de novo mutation in the LMNA gene encoding for the nuclear structural protein lamin A. The lamin family of proteins are thought to be involved in nuclear stability, chromatin structure and gene expression and this leads to heavy effects on the regulation and functionality of the cell machinery. The functional role of the large-conductance calcium-activated potassium channels (BKCa) is still unclear, but has been recently described a strong relationship with their membrane expression, progerin nuclear levels and the ageing process. In this study, we found that: i) the outward potassium membrane current amplitude and the fluorescence intensity of the BKCa channel probe showed higher values in human dermal fibroblast obtained from patients affected by HGPS if
Hutchinson-Gilford progeria syndrome (HGPS) is an extremely rare genetic disorder wherein symptoms resembling aspects of aging are manifested at a very early age. It is a genetic condition that occurs due to a de novo mutation in the LMNA gene encoding for the nuclear structural protein lamin A. The lamin family of proteins are thought to be involved in nuclear stability, chromatin structure and gene expression and this leads to heavy effects on the regulation and functionality of the cell machinery. The functional role of the large-conductance calcium-activated potassium channels (BKCa) is still unclear, but has been recently described a strong relationship with their membrane expression, progerin nuclear levels and the ageing process. In this study, we found that: i) the outward potassium membrane current amplitude and the fluorescence intensity of the BKCa channel probe showed higher values in human dermal fibroblast obtained from patients affected by HGPS if
textbf{BACKGROUND}$: Hutchinson-Gilford progeria syndrome (HGPS) is a fatal sporadic autosomal dominant premature ageing disease caused by single base mutations that optimise a cryptic splice site within exon 11 of the $\textit{LMNA}$ gene. The resultant disease-causing protein, progerin, acts as a dominant negative. Disease severity relies partly on progerin levels. $\textbf{METHODS AND RESULTS}$: We report a novel form of somatic mosaicism, where a child possessed two cell populations with different HGPS disease-producing mutations of the same nucleotide-one producing severe HGPS and one mild HGPS. The proband possessed an intermediate phenotype. The mosaicism was initially discovered when Sanger sequencing showed a c.1968+2T,A mutation in blood DNA and a c.1968+2T,C in DNA from cultured fibroblasts. Deep sequencing of DNA from the probands blood revealed 4.7% c.1968+2T,C mutation, and 41.3% c.1968+2T,A mutation. $\textbf{CONCLUSIONS}$: We hypothesise that the germline mutation was ...
Aging affects all people and is a complex process involving both genetic and environmental factors in a way that is not yet completely understood. Studies of premature aging syndromes might be helpful to acquire further clues to understand the molecular mechanisms explaining how aging occurs. Hutchinson-Gilford progeria syndrome (HGPS or progeria) is a genetic disease causing segmental premature aging in children, with an approximated incidence of 1 in 20 million individuals. Children affected by progeria appear normal at birth, but they begin developing symptoms of disease within the first years of life. Symptoms of HGPS include severe growth retardation, scleroderma-like skin changes, bone and tooth abnormalities, and loss of hair and body fat. The children with progeria die prematurely at a median age of 14.6 years, due to complications from cardiovascular disease and atherosclerosis ...
Hutchinson-Gilford Progeria Syndrome is a very rare genetic condition, causing greatly accelerated ageing. There is a genetic test, but, as of May 2013, no cure.
the Hutchinson-Gilford progeria syndrome is a rare genetic condition that affects an estimated 1 in 8 million children. It is characterized by excessive
Hutchinson-Gilford progeria syndrome is a genetic condition characterized by the dramatic, rapid appearance of aging beginning in childhood. Explore symptoms, inheritance, genetics of this condition.
Hutchinson-Gilford progeria syndrome (HGPS) is a genetic disorder displaying features reminiscent of premature senescence caused by germline mutations in the LMNA gene encoding lamin A and C, essential components of the nuclear lamina. By studying a family with homozygous LMNA mutation (K542N), we showed that HGPS can also be caused by mutations affecting both isoforms, lamin A and C. Here, we aimed to elucidate the molecular mechanisms underlying the pathogenesis in both, lamin A- (sporadic) and lamin A and C-related (hereditary) HGPS. For this, we performed detailed molecular studies on primary fibroblasts of hetero- and homozygous LMNA K542N mutation carriers, accompanied with clinical examinations related to the molecular findings. By assessing global gene expression we found substantial overlap in altered transcription profiles (13.7%; 90/657) in sporadic and hereditary HGPS, with 83.3% (75/90) concordant and 16.7% (15/90) discordant transcriptional changes. Among the concordant ones we ...
Available online at www.ijpsdr.com International Journal of Pharmaceutical Sciences and Drug Research 2014; 6(4): 253-262 Review Article ISSN: 0975-248X CODEN (USA): IJPSPP Hutchinson-Gilford Progeria Syndrome: A Prematurely Aging Disorder Ahsas Goyal*, Neetu Agrawal, Bhupesh C. Semwal, Yogesh Murti Institute of Pharmaceutical Research, GLA University, Mathura-281406, Uttar Pradesh, India ABSTRACT Hutchinson-Gilford Progeria Syndrome (HGPS) is an extremely rare genetic disorder characterized by premature aging, involving aberrant splicing of the LMNA gene, resulting in the production of a disease-causing mutant lamin A protein called progerin. Clinical manifestations are evident by the first or second year of life and include the physical characteristics usually associated with the elderly. Because neither parent carries or expresses the mutation, each case is believed to represent a sporadic, new mutation that happens most notably in a single sperm or egg immediately prior to conception. ...
Progeria ( /proʊˈdʒɪəriə/)[1], also called Hutchinson-Gilford progeria syndrome[2][3] and HGPS progeria syndrome[3] is a very rare genetic disorder. Children born with progeria show symptoms which are like aging.[4] This can include skin wrinkles and grey hair or baldness.[1] Progeria is one of several progeroid syndromes.[5] The word progeria comes from the Greek words pro (πρό), meaning before or premature, and gēras (γῆρας), meaning old age.[6] It is very rare, only 1 child in every 8 million live births.[7] People with progeria usually only live to their mid teens to early twenties.[8][9] It is a genetic condition that occurs as a new mutation. It is rarely inherited, as people with the condition do not usually live long enough to have children. Scientists are studying progeria because it might reveal clues about the normal process of aging.[10][11][12] Progeria was first described in 1886 by Jonathan Hutchinson.[13] It was also described independently in 1897 by ...
Hutchinson-Gilford progeria syndrome (HGPS) is an extremely rare hereditary disease that affects the skin, musculoskeletal system, and vasculature. HGPS is characterized by signs of premature aging.
Hutchinson-Gilford progeria syndrome (HGPS) is an extremely rare hereditary disease that affects the skin, musculoskeletal system, and vasculature. HGPS is characterized by signs of premature aging.
Lamins are type V intermediate filaments and represent the major constituent of the nuclear lamina. Mutations in the laminA/C gene as well as in other nuclear envelope associated proteins lead to a series of human genetic disorders, so-called laminopathies. The most prominent laminopathy is the Hutchinson-Gilford progeria syndrome (HGPS). HGPS patients appear prematurely aged developing aging-related conditions such as osteoporosis, loss of subcutaneous fat and cardiovaskular disease already during childhood. Many of the HGPS patients contain a single point mutation in the lamin A/C gene wh ...
PRG Science & Technology Co., Ltd. (PRG S&T) is developing Progerinin (SLC-D011) for the treatment of the rare aging diseases Hutchinson-Gilford Progeria Syndrome (HGPS) and Werner Syndrome (WS).. Progerin, an abnormal splice variant of the inner nuclear membrane protein lamin A is implicated in the pathology of HGPS and WS. It is believed that the extremely strong binding between lamin A and progerin is responsible for the nuclear abnormality phenotype observed in HGPS. WS is caused by functional defect of WRN, RecQ4L DNA helicase and rapid accumulation of progerin in WRN deficient condition is thought to be the cause of premature aging in WS. PRG S&T has shown that Progerinin binds specifically to progerin reduces its expression in both HGPS and WS cells, Progerinin further prevents progerin-lamin A in HGPS cells. In a progeria mouse model (LmnaG609G/G609G), treatment with Progerinin via intraperitoneal (i.p) injection (20 mg/kg, twice per week) could increase the body weight and extend the ...
Indication: Hutchinson-Gilford Progeria Syndrome PDUFA action date: 20 November NDA - First Review. Having previously failed in treating myelodysplastic syndrome (MDS), breast cancer, brain cancer, and non-small cell lung cancer, an approval for Eiger BioPharmaceuticals, Inc.s Zokinvy (lonafarnib) for Hutchinson-Gilford progeria syndrome the (HGPS) would be the breakthrough the drug needs, say Biomedtracker analysts. (Also see Eiger Shifts Focus After Phase II Failure In PAH - Scrip, 16 Jan, 2018.). HGPS is a rare genetic disorder with symptoms that resemble aspects of aging but at an early age. Though there is a heritable form, progeria usually occurs as a new point mutation in the LMNA gene, with a frequency of one per 8 million live births.. Eiger began a rolling NDA for Zokinvy, a farnesyl transferase inhibitor (FTI), last December, which it completed in March; the FDA has given a 20 November PDUFA date. The product also has breakthrough therapy designation for the treatment of ...
The Michaelis Laboratorys research goal is to dissect fundamental cellular processes relevant to human health and disease, using yeast and mammalian cell biology, biochemistry and high-throughput genomic approaches. Our team studies the cell biology of lamin A and its role in the premature aging disease Hutchinson-Gilford progeria syndrome (HGPS). Other research focuses on the core cellular machinery involved in recognition of misfolded proteins. Understanding cellular protein quality control machinery will ultimately help researchers devise treatments for protein misfolding diseases in which degradation is too efficient or not enough.. Research Areas: biochemistry, cell biology, protein folding, lamin A, aging, genomics, Hutchinson-Gilford progeria syndrome, yeast ...
HUTCHINSONILFORD PROGERIA SYNDROME REVIEW OF THE PHENOTYPE PDF - Establishing the detailed phenotype of Hutchinson-Gilford progeria syndrome is important because advances in understanding this syndrome may offer
The nuclear lamina is an intermediate filament network that underlies the inner nuclear membrane and ensures that the nuclear functions are able to undergo normal processes. The transport between the cytoplasm and the nucleus, the role of maintaining chromatin, and therefore the epigenetic profile of the cell are also regulated by the nuclear lamina as well as DNA replication and DNA repair. Mutations in the gene that encodes the nuclear lamina protein, lamin A, cause more than 18 tissue-specific diseases including Hutchinson-Gilford progeria syndrome (HGPS), which is manifested with tissue-specific mechanisms of ageing. Children affected by HGPS die of myocardial infarction or stroke by the time they are 16 years old and their vasculature is characterized by stiff calcified arteries and the loss of VSMCs. Since lamin A is made from a precursor protein, prelamin A, HGPS affected children have the mutation that deletes key amino acid sequences that are required for the final posttranslational ...
Alteration in the immune system is one of the most profound aspects of aging. Progressive changes in the number of B lymphocyte progenitors during aging have been reported but the underlying mechanisms are still elusive. A heterozygous G608G mutation in the LMNA gene leads to a deletion of 50 amino acids in lamin A protein, termed progerin, and is the predominant cause of Hutchinson-Gilford progeria syndrome (HGPS). Lack of Zmpste24, a metalloproteinase responsible for prelamin A processing, leads to progeroid features resembling HGPS. Therefore Zmpste24-deficient mice provide an ideal mouse model to study the impact of lamin A and (premature) aging on the aging-related decline of B lymphopoiesis. Analysis of bone marrow (BM) nucleated cells revealed a decline of early B cell progenitors in Zmpste24−/− mice. BM transplantation in a congenic strain completely rescued the defects in B lymphopoiesis, indicating that the decline in B cell progenitors in Zmpste24−/− mice is attributable to defective
El Centro Nacional de Biotecnología es un centro estratégico del Consejo Superior de Investigaciones Científicas con un objetivo mixto académico y de transferencia de tecnología en el área de la Biotecnología.
Hutchinson-Gilford progeria syndrome (HGPS) is caused by a point mutation in the LMNA gene that activates a cryptic donor splice site and yields a truncated form of prelamin A called progerin. Small amounts of progerin are also produced during normal aging. Studies with mouse models of HGPS have allowed the recent development of the first therapeutic approaches for this disease. However, none of these earlier works have addressed the aberrant and pathogenic LMNA splicing observed in HGPS patients because of the lack of an appropriate mouse model. Here, we report a genetically modified mouse strain that carries the HGPS mutation. These mice accumulate progerin, present histological and transcriptional alterations characteristic of progeroid models, and phenocopy the main clinical manifestations of human HGPS, including shortened life span and bone and cardiovascular aberrations. Using this animal model, we have developed an antisense morpholino-based therapy that prevents the pathogenic Lmna ...
Nuclear lamins, also known as Class V intermediate filaments, are fibrous proteins providing structural function and transcriptional regulation in the cell nucleus. Nuclear lamins interact with membrane-associated proteins to form the nuclear lamina on the interior of the nuclear envelope. Lamins are present in all members of the kingdom Animalia (Metazoa), but are not found in unicellular organisms, plants, or fungi. Lamin proteins are involved in the disassembling and reforming of the nuclear envelope during mitosis, the positioning of nuclear pores, and programmed cell death. Mutations in lamin genes can result in laminopathies, some of which are potentially lethal disorders. Nuclear lamins were first identified using electron-microscopy. However, they were not recognized as vital components of nuclear structural support until 1975. During this time period, investigations of rat liver nuclei revealed that lamins have an architectural relationship with chromatin and nuclear pores. Later in ...
My laboratory is interested in why and how we age. Specifically, we focus on studying molecular mechanisms of Hutchinson-Gilford progeria syndrome (HGPS), a premature aging disease, and exploring the potential connections between HGPS and normal aging. Children with HGPS die at their early teens due to heart attack or stoke. Approximately 90% of the HGPS cases are causedby a de novo mutation at 1824 position of the lamin A gene (C1824T, G608G). This mutation does not affect the coded amino acid, but partially activates a cryptic splice donor site in the exon 11, leading to the production of a mutant lamin A mRNA that contains an internal deletion of 150 base pairs. This is then translated into a lamin A mutant protein missing 50 amino acids near the C-terminus, termed progerin. ...
JH4 blocks progerin-induced lamin A aggregation in ER during the G2/M phase. Because many of the JH4-responsive genes shown in Supplemental Table 4 and Figure 4B are involved in cell-cycle and chromosome regulation and progerin induces cell-cycle arrest at the G2/M checkpoint (Figure 6E), we examined the effect of JH4 on the behavior of lamin A at the G2/M phase. Dispersal of lamin A upon treatment with Taxol (paclitaxel) was observed in young, but not aged, cells. Rather, lamin A surrounded chromosomal or nuclear DNA (Supplemental Figure 10A, white arrows). However, treatment with JH4 could promote lamin A elimination in aged cells (Supplemental Figure 10A, yellow arrows). We also observed that progerin-induced lamin A aggregation in nocodazol- or Taxol-treated cells was abolished by JH4, but not by FTI-277 (Supplemental Figure 10, B and C). To gain further insight into this observation, we analyzed the localization of progerin in nocodazol- or Taxol-treated cells. Cytoplasmic aggregates in ...
Researchers at the Centro Nacional de Investigaciones Cardiovasculares (CNIC) and the Universidad de Oviedo have discovered a new molecular mechanism involved in the premature development of atherosclerosis in mice with Hutchinson-Gilford progeria syndrome (HGPS). Moreover, the results, published in EMBO Molecular Medicine, identify a potential therapeutic target for this severe genetic disease, which is characterized by the premature onset of cardiovascular disease and early death, usually from a heart attack or stroke, between the ages of 6 and 20 years.. Progeria is very rare genetic disease caused by a mutation in the LMNA gene. The disease affects an estimated 400 people worldwide. HGPS patients show accelerated aging linked to a high risk of cardiovascular disease. In the words of study leader Vicente Andrés, studying this disease brings us closer to a possible treatment for disease victims and can provide important information about normal physiological aging and the factors that ...
Hi, Im Harry Crowther, Im 18 years old and I have an extremely rare genetic disorder known as Atypical Progeria Syndrome (Non Classical Progeria) whereby I have a defect with the LAMIN A/C gene (LMNA). Though not to be confused with the classical Hutchinson Guilford Progeria Syndrome (HGPS) - both are Premature Aging Disorders. I was diagnosed in the USA aged 7 years old. Together with my Mum I keep this blog. Hope you enjoy my story.. ...
Hi, Im Harry Crowther, Im 18 years old and I have an extremely rare genetic disorder known as Atypical Progeria Syndrome (Non Classical Progeria) whereby I have a defect with the LAMIN A/C gene (LMNA). Though not to be confused with the classical Hutchinson Guilford Progeria Syndrome (HGPS) - both are Premature Aging Disorders. I was diagnosed in the USA aged 7 years old. Together with my Mum I keep this blog. Hope you enjoy my story.. ...
B-type lamins are present in every cell. B type lamins, lamin B1 and B2, are expressed from the LMNB1 and LMNB2 genes on 5q23 ... A-type lamins are only expressed following gastrulation. Lamin A and C are the most common A-type lamins and are splice ... Most types are cytoplasmic, but one type, Type V is a nuclear lamin. Unlike microtubules, IF distribution in cells show no good ... "type V" nuclear lamin. In addition, a few other diverse types of Eukaryotes have lamins, suggesting an early origin of the ...
Antibodies against lamins are detected in the sera of some individuals with autoimmune diseases. A-type lamins promote genetic ... Most lamin B mutations appear to be lethal with mutations in lamin B1 causing death at birth in mice. In 2006, lamin B2 ... The inability to adequately repair DNA damages when A-type lamins are defective is likely responsible for some of the aspects ... Cao H, Hegele RA (2002). "Nuclear lamin A/C R482Q mutation in Canadian kindreds with Dunnigan-type familial partial ...
Vertebrate lamins consist of two types, A and B. Through alternate splicing, this gene encodes three type A lamin isoforms. ... LMNA, also known as Lamin A/C is a protein that in humans is encoded by the LMNA gene. Lamin A/C belongs to the lamin family of ... Mounkes LC, Burke B, Stewart CL (2001). "The A-type lamins: nuclear structural proteins as a focus for muscular dystrophy and ... Cao H, Hegele RA (2002). "Nuclear lamin A/C R482Q mutation in Canadian kindreds with Dunnigan-type familial partial ...
Muscular LMNA interacting protein has a number of aliases including MLIP, C6orf142, CIP and Muscle-enriched A-type Lamin- ... muscle-enriched A-type lamin-interacting protein) leads to cardiac hyperactivation of Akt/mammalian target of rapamycin (mTOR) ... "Identification of a novel muscle A-type lamin-interacting protein (MLIP)". The Journal of Biological Chemistry. 286 (22): 19702 ... It interacts with the nuclear envelope proteins lamin A/C, which is what led to its discovery. It also interacts with Islet1 ...
Furukawa K, Kondo T (Feb 1998). "Identification of the lamina-associated-polypeptide-2-binding domain of B-type lamin". ... Furukawa K, Kondo T (Feb 1998). "Identification of the lamina-associated-polypeptide-2-binding domain of B-type lamin". ... "Lamina-associated polypeptide 2alpha binds intranuclear A-type lamins". Journal of Cell Science. 113 Pt 19 (19): 3473-84. PMID ... "Lamina-associated polypeptide 2alpha binds intranuclear A-type lamins". Journal of Cell Science. 113 Pt 19 (19): 3473-84. PMID ...
... has been shown to be involved in the progression of some types of cancers, such as osteosarcoma and head and neck ... Lamin A and prelamin A Akt. GRCh38: Ensembl release 89: ENSG00000165887 - Ensembl, May 2017 GRCm38: Ensembl release 89: ... is preferentially expressed in type 1 skeletal muscle fibers and is markedly induced by denervation". Lab. Invest. 82 (5): 645- ... skeletal muscles tended towards a more slower fiber type distribution, with longer resting sarcomere length, decreased fiber ...
Mounkes LC; Kozlov S (2003). "A progeroid syndrome in mice is caused by defects in A-type lamins" (PDF). Nature. 423 (6937): ... While there may be some validity to the idea that for various types of specific damage detailed below that are by-products of ... For a critique of the Rate of Living Hypothesis see Living fast, dying when?) With respect to specific types of chemical damage ... Horvath S (2013). "DNA methylation age of human tissues and cell types". Genome Biology. 14 (10): R115. doi:10.1186/gb-2013-14- ...
A large pool of LC3 is present in the nucleus of a variety of different cell types. In response to starvation, nuclear LC3 is ... Nuclear LC3 interacts with lamin B1, and participates in the degradation of nuclear lamina. LC3 is also enriched in nucleoli ... "Post-translational modifications of three members of the human MAP1LC3 family and detection of a novel type of modification for ...
In progeria, the inability to adequately repair DNA damages due to defective A-type lamin may cause aspects of premature aging ... lamin A, along with lamin B1, lamin B2, and lamin C, makes up the nuclear lamina, which provides shape and stability to the ... Cao H, Hegele RA; Hegele (2002). "Nuclear lamin A/C R482Q mutation in Canadian kindreds with Dunnigan-type familial partial ... It is caused by mutations in the LMNA (lamin A protein) gene on chromosome 1; the mutated form of lamin A is commonly known as ...
Type V consists of the nuclear lamins, and type VI consists of the protein nestin. The type IV intermediate filament genes all ... Types I and II are the keratins which are expressed in epithelia. Type III contains the proteins vimentin, desmin, peripherin ... The type III intermediate filament subunit, vimentin, is expressed in developing neurons and a few very unusual neurons in the ... The type VI intermediate filament protein nestin is expressed in developing neurons and glia. Nestin is considered a marker of ...
The lamins are type V intermediate filaments which can be categorized as either A-type (lamin A, C) or B-type (lamin B1, B2) ... LA are considered homologous to lamin A and LIII as a B-type lamin. A fourth type exists and is germ cell specific. In the ... the only lamins present are B-type lamins. In further stages, the expression pattern of lamin B1 decreases and there is a ... In the latter case as well it is the B-type lamins that are expressed in the early stages. Lamin B1 reaches the highest ...
A-type lamins promote genetic stability by maintaining levels of proteins which have key roles in NHEJ and HR.[77] Mouse cells ... Defects in Lamin A/C[edit]. Lamin is required at the inner nuclear membrane to ensure the nucleus keeps its shape. Mutations in ... There are eight types of XP (XP-A through XP-G), plus a variant type (XP-V), all categorized based on the genetic cause. XP can ... "A dual role for A-type lamins in DNA double-strand break repair". Cell Cycle. 10 (15): 2549-60. doi:10.4161/cc.10.15.16531. PMC ...
A-type lamins promote genetic stability by maintaining levels of proteins that have key roles in the DNA repair processes of ... "A dual role for A-type lamins in DNA double-strand break repair". Cell Cycle. 10 (15): 2549-60. doi:10.4161/cc.10.15.16531. PMC ... The initial study of this type, by Hart and Setlow, showed that the ability of skin fibroblasts of seven mammalian species to ... Numerous studies of this type have indicated that oxidative damage to DNA is particularly important. The loss of expression of ...
"A dual role for A-type lamins in DNA double-strand break repair". Cell Cycle. 10 (15): 2549-60. doi:10.4161/cc.10.15.16531. PMC ... It is involved in the processing of lamin A. Defects in the ZMPSTE24 gene lead to similar laminopathies as defects in lamin A, ... As shown by Liu et al., lack of Zmpste24 prevents lamin A formation from its precursor farnesyl-prelamin A. Lack of ZMPSTE24 ...
In HGPS, the inability to adequately repair DNA damages due to defective A-type lamin may cause aspects of premature aging (see ... There are eight types of XP (XP-A through XP-G), plus a variant type (XP-V), all categorized based on the genetic cause. XP can ... A-type lamins promote genetic stability by maintaining levels of proteins which have key roles in NHEJ and HR. Mouse cells ... "A dual role for A-type lamins in DNA double-strand break repair". Cell Cycle. 10 (15): 2549-60. doi:10.4161/cc.10.15.16531. PMC ...
A-type lamins promote genetic stability by maintaining levels of proteins that have key roles in the repair processes of non- ... "A dual role for A-type lamins in DNA double-strand break repair". Cell Cycle. 10 (15): 2549-2560. doi:10.4161/cc.10.15.16531. ... Additionally, these individuals have much lower incidences of age-related diseases such as type 2 diabetes and cancer. Lastly, ... Patients with HGPS have cellular defects, specifically in the lamin proteins, which regulate the organization of the lamina and ...
A-type lamins promote genetic stability by maintaining levels of proteins that have key roles in non-homologous end joining and ... It is located on the long arm of the chromosome 1 (1q21-q22) and encodes the proteins lamin A and lamin C. These are structural ... "A dual role for A-type lamins in DNA double-strand break repair". Cell Cycle. 10 (15): 2549-2560. doi:10.4161/cc.10.15.16531. ... Lamin A/C congenital muscular dystrophy (CMD) (L-CMD, congenital muscular dystrophy associated to the LMNA gene or Emery- ...
In HGPS, the inability to adequately repair DNA damages due to defective A-type lamin may cause aspects of laminopathy-based ... HGPS is caused by a point mutation in the gene that encodes lamin A protein. Lamin A promotes genetic stability by maintaining ... Those who have Werner syndrome are at an increased risk for cataracts, type 2 diabetes, different types of cancers, and ... "A dual role for A-type lamins in DNA double-strand break repair". Cell Cycle. 10 (15): 2549-2560. doi:10.4161/cc.10.15.16531. ...
Kollmar, M (29 May 2015). "Polyphyly of nuclear lamin genes indicates an early eukaryotic origin of the metazoan-type ... The DNA sequence of the protein has sections very similar to the eukaryotic keratin and lamin proteins, mostly involving the ... is that crescentin lacks certain consensus sequence elements at the ends of the rod domain which are conserved in animal lamin ...
The CaaX motif is found at the COOH-terminus of proteins, such as lamins or ras. The motif consists of a cysteine (C), two ... Taylor J, Reid T, Terry K, Casey P, Beese L (2003). "Structure of mammalian protein geranylgeranyltransferase type-I". EMBO J. ... There are at least 3 types of sites that are recognized by prenylation enzymes. ... Farnesylation is a type of prenylation, a post-translational modification of proteins by which an isoprenyl group is added to a ...
Charcot-Marie-Tooth disease, types 1 and 2. *collagenopathy, types II and XI ... LMNA: lamin A/C. *MPZ: myelin protein zero (Charcot-Marie-Tooth neuropathy 1B) ...
"The truncated prelamin A in Hutchinson-Gilford progeria syndrome alters segregation of A-type and B-type lamin homopolymers" ( ... has also been used to show the interaction of both types of nuclear intermediate filament proteins lamins A and B1 in distinct ...
González, Jose M.; Andrés, Vicente (2011). "Synthesis, transport and incorporation into the nuclear envelope of A-type lamins ... As mutations in lamins cause the autosomal dominant form of Emery-Dreifuss muscular dystrophy, and lamins and emerin are known ... Lamins and chromatin found at the nuclear envelope are organised with the assistance of proteins embedded in the INM. INM ... For example, lamin B receptor, lamina-associated polypeptide 1 and lamina-associated polypeptide 2 are targets for different ...
"The inner nuclear membrane protein LAP1 forms a native complex with B-type lamins and partitions with spindle-associated ... More commonly known as lamina associated polypeptide 1 (LAP1), it is a type II integral membrane protein that resides in the ... Foisner R, Gerace L (1993). "Integral membrane proteins of the nuclear envelope interact with lamins and chromosomes, and ...
The only nuclear proteins known to be prenylated in mammalian cells are prelamin A- and B-type lamins. Prelamin A is ... translationally modified cysteine residue is removed from prelamin A when it is endoproteolytically processed into mature lamin ...
2000). „Lamina-associated polypeptide 2alpha binds intranuclear A-type lamins". J. Cell. Sci. ENGLAND. 113 (19): 3473-84. ISSN ... 2000). „Lamina-associated polypeptide 2alpha binds intranuclear A-type lamins.". J. Cell. Sci. 113 (19): 3473-84. PMID 10984438 ... Furukawa, K; T, Kondo (1998). „Identification of the lamina-associated-polypeptide-2-binding domain of B-type lamin". Eur. J. ... Furukawa K, Kondo T (1998). „Identification of the lamina-associated-polypeptide-2-binding domain of B-type lamin.". Eur. J. ...
Vertebrate lamins consist of two types, A and B. Through alternate splicing, this gene encodes three type A lamin isoforms.[4] ... The A-type lamins: nuclear structural proteins as a focus for muscular dystrophy and cardiovascular diseases. Trends Cardiovasc ... Biogenesis of lamin A in normal cells and the failure to generate mature lamin A in HGPS. In the setting of ZMPSTE24 deficiency ... Donadille B, Lascols O, Capeau J, Vigouroux C. Etiological investigations in apparent type 2 diabetes: when to search for lamin ...
Cao H, Hegele RA (January 2000). "Nuclear lamin A/C R482Q mutation in canadian kindreds with Dunnigan-type familial partial ... Some types of polyunsaturated fatty acids (omega-3) may moderate the progression of insulin resistance into type 2 diabetes,[86 ... "Type 2 diabetes: Risk factors". Mayo Clinic. Retrieved 21 December 2011.. *^ a b c d Milner KL, van der Poorten D, Trenell M, ... People who already have type 2 diabetes may see a small increase in levels if they take 2 or 2-1/2 cups of coffee per day.[90] ...
"Mistargeting of B-type lamins at the end of mitosis: implications on cell survival and regulation of lamins A/C expression". ... The nuclear lamina is composed mostly of lamin proteins. Like all proteins, lamins are synthesized in the cytoplasm and later ... The destruction of the lamin networks is controlled by specialized apoptotic proteases called caspases, which cleave the lamin ... Lamins found on the cytosolic face of the membrane, such as emerin and nesprin, bind to the cytoskeleton to provide structural ...
... a type VI intermediate filament protein. Limited co-assembly in vitro to form heteropolymers with type III vimentin and type IV ... Nestin is of high molecular weight (240kDa) with a terminus greater than 500 residues (compared to cytokeratins and lamins with ... Nestin is expressed by many types of cells during development, although its expression is usually transient and does not ... In mixtures, nestin preferentially co-assembles with purified vimentin or the type IV IF protein internexin to form heterodimer ...
Six types (1-6) have been described. Types 1-5 are inherited in an autosomal dominant fashion. Type 1 (Kobberling variety, FPL1 ... Mutations associated with FPL have been reported in LMNA (lamin A/C), PPARG (PPARγ), AKT2 (AKT serine/threonine kinase 2), ... Type 3 is due to mutations in the PPARG gene. It is rare with approximately 30 cases reported to date. It is similar to type 2 ... Type 4 is due to mutations in the PLIN1 gene. It is rare with only a small number of cases reported. Fat loss tends to affect ...
... phenotypic overlap among otopalatodigital syndrome type II, boomerang dysplasia, atelosteogenesis type I and type III, and ... Nishimura G, Horiuchi T, Kim OH, Sasamoto Y (1997). "Atypical skeletal changes in otopalatodigital syndrome type II: ... "Lethal bone dysplasia in a fetus with manifestations of Atelosteogenesis type I and Boomerang dysplasia". Am J Med Genet. 47 (4 ... including boomerang dysplasia and atelosteogenesis type I.[6][7][8] ...
It is characterized by a white blood cell type known as a neutrophil whose nucleus is hyposegmented.[citation needed] ... Is a benign dominantly inherited defect of terminal neutrophil differentiation as a result of mutations in the lamin B receptor ... Pelger-Huët anomaly is a blood laminopathy associated with the lamin B receptor.[1] ... "Mutations in the gene encoding the lamin B receptor produce an altered nuclear morphology in granulocytes (Pelger-Huët anomaly ...
Type 1/2. (Keratin,. Cytokeratin). Epithelial keratins. (soft alpha-keratins). *type I/chromosome 17 *10 ...
lamin binding. • amyloid-beta binding. • protease binding. • glycosaminoglycan binding. • type 5 metabotropic glutamate ... type 8 metabotropic glutamate receptor binding. • signaling receptor activity. • macromolecular complex binding. • cupric ion ...
The judges unanimously found the second accused, Lamin Khalifah Fhimah, not guilty of the murder charge.[20] Fhimah was freed ... Marwan Khreesat was released for lack of evidence by German police even though a barometric timer of the type used to detonate ... His co-accused, Lamin Khalifah Fhimah, was found not guilty and was acquitted.[2] ... Megrahi and Lamin Khalifah Fhimah, denied all charges against them. The full charges included the names of the murdered 259 ...
Mutation of the lamin AC gene is also associated with fibrosis of the atria that can lead to atrial fibrillation. ... "FDA approves Xarelto to prevent stroke in people with common type of abnormal heart rhythm". FDA. Archived from the original on ... Finally, nicotine induces the formation of patterns of collagen type III in the atrium and has profibrotic effects. All this ... which may greatly increase the risk of stroke and alter recommendations for the appropriate type of anticoagulation), left and ...
Certain types of cancer can arise from such mutations.[6] Mitosis occurs only in eukaryotic cells. Prokaryotic cells, which ... At the beginning of prometaphase in animal cells, phosphorylation of nuclear lamins causes the nuclear envelope to disintegrate ... Have the Polygonum and Allium types been rightly established? Ann Bot (Rome) 45: 81-117. [p. 85: "Already in 1887, Weismann ... In relation to the forms of mitosis, closed intranuclear pleuromitosis seems to be the most primitive type, as it is the more ...
"Mistargeting of B-type lamins at the end of mitosis: implications on cell survival and regulation of lamins A/C expression". J ... 2000). "Nuclear Lamins A and B1: Different Pathways of Assembly during Nuclear Envelope Formation in Living Cells". Journal of ... Mounkes LC, Stewart CL (2004). "Aging and nuclear organization: lamins and progeria". Current Opinion in Cell Biology. 16: 322- ... Stuurman N, Heins S, Aebi U (1998). "Nuclear lamins: their structure, assembly, and interactions". J Struct Biol. 122 (1-2): 42 ...
De Jonghe P, Jordanova AK (2011-10-27). Charcot-Marie-Tooth Neuropathy Type 2E/1F. NBK1187.. In GeneReviews ... Bird TD (30 January 2014). Charcot-Marie-Tooth Neuropathy Type 2. PMID 20301462. NBK1285.. In GeneReviews ... "Further evidence that neurofilament light chain gene mutations can cause Charcot-Marie-Tooth disease type 2E". Annals of ... "Charcot-Marie-Tooth Neuropathy Type 1". In Pagon RA, Bird TD, Dolan CR, et al. GeneReviews™ [Internet]. Seattle WA: University ...
Types of muscle are striated muscle (such as skeletal muscle and cardiac muscle), obliquely striated muscle (found in some ... This study concludes that there is no clear relationship between fiber-type composition and in vivo muscle tension, nor was ... Athletes across a spectrum of sporting events are particularly interested to know what type of training protocol will result in ... Again, researchers are not completely clear about the molecular mechanisms of change, and an alteration of fiber-type ...
New electrocardiographic criteria for diagnosis of type-1 Andersen-Tawil syndrome". Current Cardiology Reviews. 10 (3): 222-228 ... Lamin B1 duplications cause autosomal dominant leukodystrophy. Nat Genet. 2006 Oct; 38(10):1114-23. ... five of which are dominant negative mutations that mask the wild-type allele, resulting in a loss-of-function of that gene.[6] ...
"Identification and overlapping expression of multiple unconventional myosin genes in vertebrate cell types". Proceedings of ... "Cleavage of human and mouse cytoskeletal and sarcomeric proteins by human immunodeficiency virus type 1 protease. Actin, ...
Ling K, Doughman RL, Firestone AJ, Bunce MW, Anderson RA (Nov 2002). "Type I gamma phosphatidylinositol phosphate kinase ... 1y19: Structural basis for phosphatidylinositol phosphate kinase type I-gamma binding to talin at focal adhesions ... "Recruitment and regulation of phosphatidylinositol phosphate kinase type 1 gamma by the FERM domain of talin". Nature. 420 ( ... "Layilin, a novel talin-binding transmembrane protein homologous with C-type lectins, is localized in membrane ruffles". The ...
... multiple endocrine neoplasia type 1,[17] inv(16) AML[18] and Hutchinson-Gilford progeria syndrome.[19] ... "Recurrent de novo point mutations in lamin a cause Hutchinson-Gilford progeria syndrome". Nature. 423 (6937): 293-8. Bibcode: ... "Positional Cloning of the Gene for Multiple Endocrine Neoplasia-Type 1". Science. 276 (5311): 404-7. doi:10.1126/science. ... which has sought to identify and understand the genetic variations that influence the risk of developing type 2 diabetes. ...
Cell types. Cells are of two types: eukaryotic, which contain a nucleus, and prokaryotic, which do not. Prokaryotes are single- ... But some of the subunit protein of intermediate filaments include vimentin, desmin, lamin (lamins A, B and C), keratin ( ... A different type of flagellum is found in archaea and a different type is found in eukaryotes. ... Cell types differ both in appearance and function, yet are genetically identical. Cells are able to be of the same genotype but ...
"Mistargeting of B-type lamins at the end of mitosis: implications on cell survival and regulation of lamins A/C expression". ... The nuclear lamina is composed mostly of lamin proteins. Like all proteins, lamins are synthesized in the cytoplasm and later ... The destruction of the lamin networks is controlled by specialized apoptotic proteases called caspases, which cleave the lamin ... In most types of granulocyte, a white blood cell, the nucleus is lobated and can be bi-lobed, tri-lobed or multi-lobed. ...
Type 1/2. (Keratin,. Cytokeratin). Epithelial keratins. (soft alpha-keratins). *type I/chromosome 17 *10 ...
lamin tasu ralan tadau wagu tokou onu/nu tapui Kadazan iso duvo tohu apat tuhun hamin tasu lahan tadau vagu tokou onu,. nunu ... Very broadly, one can divide the Austronesian languages into three groups: Philippine-type languages, Indonesian-type languages ... K-type) o. kasi. lua. kolu. fa. lima. ogo. fiku. valu. iva. sefulu ... Unlike the Philippine type, these languages mostly tend towards verb-second word-orders. A number of languages, such as the ...
Simos G, Maison C, Georgatos SD (1996). "Characterization of p18, a component of the lamin B receptor complex and a new ... correlates with wild-type pRb function". Genes Dev. 8 (24): 2939-52. doi:10.1101/gad.8.24.2939. PMID 8001816.. الوسيط , ...
Initially, a Glu1425Gly mutation in ANK2 was found to cause dominantly-inherited long QT syndrome, type 4, cardiac arrhythmia. ... type 4, which can be described as an atypical arrhythmia syndrome with bradycardia, atrial fibrillation, conduction block, ... "Ankyrin-B mutation causes type 4 long-QT cardiac arrhythmia and sudden cardiac death". Nature. 421 (6923): 634-9. doi:10.1038/ ... "Ankyrin-B mutation causes type 4 long-QT cardiac arrhythmia and sudden cardiac death". Nature. 421 (6923): 634-9. doi:10.1038/ ...
As a type II hair keratin, it is a basic protein which heterodimerizes with type I keratins to form hair and nails. The type II ... "Sequence data and chromosomal localization of human type I and type II hair keratin genes". Exp Cell Res. 220 (2): 357-62. doi: ... Keratin, type II cuticular Hb1 is a protein that in humans is encoded by the KRT81 gene.[5][6][7] ... 2000). "Characterization of a 300 kbp region of human DNA containing the type II hair keratin gene domain". J. Invest. Dermatol ...
TypesEdit. There are also significant differences between prokaryotic and eukaryotic origins of replication: *Most bacteria ... In humans an origin of replication has been originally identified near the Lamin B2 gene on chromosome 19 and the ORC binding ...
Lamin A Non-homologous end joining, Homologous recombination. increased DNA damage and chromosome aberrations; progeria; ... Tyrosinemia type II. *punctate: Acrokeratoelastoidosis of Costa. *Focal acral hyperkeratosis. *Keratosis punctata palmaris et ... lack of Zmpste24 prevents lamin A formation and causes progeroid phenotypes in mice and humans, increased DNA damage and ...
... is the myosin type responsible for producing muscle contraction in muscle cells in most animal cell types. It is also found in ... Some isoforms have specialized functions in certain cell types (such as muscle), while other isoforms are ubiquitous. The ...
This type of ideogram is generally used in genome browsers (e.g. Ensembl, UCSC Genome Browser). ... LMNA: lamin A/C. *LOC645166 encoding protein Lymphocyte-specific protein 1 pseudogene ... FRA1J encoding protein Fragile site, 5-azacytidine type, common, fra(1)(q12) ... This type of ideogram represents actual relative band length observed under a microscope at the different moments during the ...
Type B / Class II). Acidic CK. (Type A / Class I) HMWCK. "squamous keratins" CK-1. CK-2. CK-3. CK-4. CK-5. CK-6. CK-9. CK-10. ... There are two categories of cytokeratins: the acidic type I cytokeratins and the basic or neutral type II cytokeratins. Within ... Types[edit]. Micrograph showing low molecular weight cytokeratin (LMWCK) staining of intermediate trophoblast (placental tissue ... sequence identity among cytokeratins of the same type and around 30% between cytokeratins of different type) with non-α-helical ...
Identification of the lamina-associated-polypeptide-2-binding domain of B-type lamin.. Furukawa K1, Kondo T. ... Lamina-associated polypeptide (LAP)2, which directly interacts with B-type lamins and chromosomes, is an integral membrane ... Publication type, MeSH terms, Substances. Publication type. *Research Support, Non-U.S. Govt ... we examined which domain of B-type lamin interacts with LAP2 by means of a binding assay with bacterially expressed proteins ...
Type A Insulin Resistance Syndrome Revealing a Novel Lamin A Mutation. Jacques Young, Louise Morbois-Trabut, Béatrice Couzinet ... Type A Insulin Resistance Syndrome Revealing a Novel Lamin A Mutation. Jacques Young, Louise Morbois-Trabut, Béatrice Couzinet ... Type A Insulin Resistance Syndrome Revealing a Novel Lamin A Mutation Message Subject (Your Name) has forwarded a page to you ... The familial partial lipodystrophy of the Dunnigan type, one of the diseases due to mutations in the lamin A/C (LMNA) gene, is ...
Meaning of lamin type a. What does lamin type a mean? Information and translations of lamin type a in the most comprehensive ... Definition of lamin type a in the Definitions.net dictionary. ... Search for lamin type a on Amazon. *Search for lamin type a on ... What does lamin type a mean?. Definitions for lamin type a. Here are all the possible meanings and translations of the word ... Alternative searches for lamin type a:. *Search for Synonyms for lamin type a ...
Type B lamins remain associated with the integral nuclear envelope protein p58 during mitosis: implications for nuclear ... Our data provide direct, in vivo and in vitro evidence that the majority of type B lamins remain connected to nuclear membrane ... Publication type, MeSH terms, Substances. Publication type. *Research Support, Non-U.S. Govt ... This sub-assembly does not include the type A lamins which are fully solubilized during mitosis. ...
A-type lamins, primarily represented by the proteins lamin A and lamin C, are unique intermediate filaments that localize to ... The A-type lamin knockout mouse (Lmna-/-) exhibits many characteristics of striated muscle laminopathies, such as muscular ... Point mutations in lamin A have been implicated in a wide variety of human diseases, termed laminopathies, which are ... In this dissertation, I use the Lmna-/- mouse model to further dissect and understand the role of lamin A in cardiac function, ...
... known as lamins. Mutations in the LMNA gene, which encodes A-type lamins, or in the ZMPSTE24 gene, which encodes a zinc ... Molecular dissection of A-type lamin-regulated pathways. Datum: 2 oktober 2017 Locatie: Universiteit Gent, Campus Coupure, ... In summary, we show that redox balance, focal adhesion and cytoskeletal tension are affected by loss of A-type lamins. We ... Interestingly, functional validation showed that loss of A- type lamins perturbed the coordination between focal adhesion ...
Lamin A/C is necessary for the retinoblastoma protein (pRB) stabilization through unknown mechanism(s). Two oncoproteins, ... To determine if gankyrin promotes pRB destabilization in the absence of lamin A/C, we first analyzed its protein levels in Lmna ... Two findings from this study also increase the likelihood that lamin A/C functions as a tumor suppressor. First, protein levels ... These findings suggest that lamin A-mediated degradation of pRB would be gankyrin-dependent. However, effective RNAi-enforced ...
Furthermore, selective disruption of A-type lamin structures by overexpression of lamin mutants in HeLa cells caused a ... Lamina-associated polypeptide 2alpha binds intranuclear A-type lamins. T. Dechat, B. Korbei, O.A. Vaughan, S. Vlcek, C.J. ... Lamina-associated polypeptide 2alpha binds intranuclear A-type lamins. T. Dechat, B. Korbei, O.A. Vaughan, S. Vlcek, C.J. ... Lamina-associated polypeptide 2alpha binds intranuclear A-type lamins. T. Dechat, B. Korbei, O.A. Vaughan, S. Vlcek, C.J. ...
Inicio Neurología (English Edition) Emery-Dreifuss muscular dystrophy type 2: New de novo mutation in the lamin A/C ... ... Emery-Dreifuss muscular dystrophy type 2: New de novo mutation in the lamin A/C gene ... Given a suspected case of EDMD with a lack of relevant family history, we sequenced the lamin A/C gene (LMNA). The gene was ... Clinical and molecular genetic spectrum of autosomal dominant Emery-Dreifuss muscular dystrophy due to mutations of the lamin A ...
Dunnigan type familial partial lipodystrophy (FPLD2; OMIM#151660) is caused in most cases by the A-type lamin R482W mutation. ... The p.R482W substitution in A-type lamins deregulates SREBP1 activity in Dunnigan-type familial partial lipodystrophy.. [ ... These interactions involve the Ig-fold of A-type lamins and are favored upon SREBP1 binding to its DNA target sequences. We ... In contrast, both overexpression of LMNA R482W in primary human preadipocytes and endogenous expression of A-type lamins R482W ...
However, B-type lamins might `set the stage for the assembly of A-type lamins. A-type lamins are known to be architectural ... We do not yet know whether B-type lamins are direct architectural partners for A-type lamins in vivo. A- and B-type lamins have ... We have taken a fresh look at the published binding partners for A-type lamins (Table 1, Fig. 1). Some bind A-type lamins in ... However, the basis for the dependence of metazoans on B-type lamins is still unknown. A-type lamins, although dispensable ...
Recent evidence has demonstrated that lamins A and C have essential functions in protecting cells from physical damage, as well ... Thus, the degenerative nature of laminopathies is explained because these lamins are essential for maintenance of somatic ... The gene LMNA encodes the proteins lamins A and C and is implicated in nine different laminopathies - inherited diseases that ... A-type lamins: Guardians of the soma?. @article{Hutchison2004AtypeLG, title={A-type lamins: Guardians of the soma?}, author={ ...
Its major components are the A- and B-type lamins. Whereas B-type lamins are found in all mammalian cells, A-type lamin ... A-type (A, AΔ10 and C) and B-type (B1 and B2). Lamins B1 and B2 are encoded by separate genes, whereas all of the A-type lamins ... While B-type lamins are found in all nucleated somatic cells, the expression of A-type lamins is developmentally regulated. In ... only express B-type lamins (Rober et al. 1990). These findings indicate that at the cellular level, A-type lamins are ...
A-type lamins, which form stable filaments in animal cell nuclei. Mutations in A-type lamins cause a bewildering range of ... A-type lamins, which form stable filaments in animal cell nuclei. Mutations in A-type lamins cause a bewildering range of ... A-type lamins, which form stable filaments in animal cell nuclei. Mutations in A-type lamins cause a bewildering range of ... A-type lamins, which form stable filaments in animal cell nuclei. Mutations in A-type lamins cause a bewildering range of ...
... and wild-type lamin permits promoter release following tissue-specific activation. A disease-linked point mutation in lamin ... Lamin helps sequester heterochromatin at the nuclear envelope, ... and wild-type lamin permits promoter release following tissue- ... We then express at low levels in otherwise wild-type worms a lamin carrying a point mutation, Y59C, which in humans is linked ... Results: Using ablation of the unique lamin gene in C. elegans, we show that lamin is necessary for the perinuclear positioning ...
Publication types * Research Support, N.I.H., Extramural * Research Support, Non-U.S. Govt ... Interstitial telomeric loops and implications of the interaction between TRF2 and lamin A/C Differentiation. Jul-Aug 2018;102: ... Here, we review the roles of TRF2 and lamin A/C in telomere biology and consider how their interaction may relate telomere ... Keywords: Aging; Interstitial t-loops; Lamin A/C; Stem cells; T-loops; TRF2; Telomeres. ...
Drosophila possesses both lamin types, encoded by the LamC (A-type) and lamin Dm0 (B-type) genes. LamC is nested within an ... and B-type lamins. lamin Dm0 encodes the B-type lamin and has been the subject of several genetic and molecular studies (Riemer ... lamin A and lamin C. Expression of A-type lamins is limited to terminally differentiated somatic cells. Human lamin A possesses ... we tested whether expression of mutant A-type lamin in a wild-type LamC genetic background disrupts B-type lamin organization ...
Study Type :. Interventional (Clinical Trial) Estimated Enrollment :. 160 participants. Allocation:. Randomized. Intervention ... Dilated Cardiomyopathy Lamin A/C Gene Mutation Drug: ARRY-371797 (PF-07265803) Other: Placebo Phase 3 ... Patients with symptomatic lamin A/C protein (LMNA)-related cardiomyopathy Class II/III/ or Class IV defined as: ... A Study of ARRY-371797 (PF-07265803) in Patients With Symptomatic Dilated Cardiomyopathy Due to a Lamin A/C Gene Mutation ( ...
... since a wide range of diseases are induced by mutations in the gene coding for A-type lamins, globally known as laminopathies. ... Moreover, it has been demonstrated that lamins are involved in other pathological conditions, like cancer. The role of lamins ... The present work is aimed to review some interesting experimental techniques performed so far to study lamins. Scientists can ... This multidisciplinary approach has contributed to resolving the unique features of lamins and has provided a thorough insight ...
Type: Initial release. *Version 1.1: 2018-01-24. Changes: Structure summary *Version 1.2: 2018-06-20. Changes: Data collection ... Structures of the lamin A/C R335W and E347K mutants: Implications for dilated cardiolaminopathies.. Bollati, M., Barbiroli, A. ... Most of the DCM-related mutations fall in the Lamin AC gene, in particular in the Coil2B domain of the encoded protein. In this ... that have been proposed to interact/associate with lamin A/C. ... Structure of Coil 2b of human lamin. *DOI: 10.2210/pdb3V5B/pdb ...
In various differentiated Drosophila cell types, we discovered the existence of peripheral heterochromatin, similar to that ... using cell type-specific DamID we mapped genome-wide LADs, HP1a and Polycomb (Pc) domains from the central brain, Repo-positive ... the only Drosophilla cell type where LADs have previously been mapped, they are neither H3K9me2-enriched nor overlapped with ... From: The large fraction of heterochromatin in Drosophila neurons is bound by both B-type lamin and HP1a ...
Emerin and A-type lamin-deficient cells have impaired mechanotransduction. (a) Expression of the mechanosensitive genes iex-1 ... and A-type lamin-deficient cells respectively, P , 0.05 for wild-type vs. emerin-deficient and wild-type vs. A-type lamin- ... and A-type lamin-deficient cells respectively, P , 0.05 for wild-type vs. emerin-deficient and wild-type vs. A-type lamin- ... for wild-type, emerin-deficient, and A-type lamin-deficient cells, respectively, P , 0.05 for wild-type vs. A-type lamin- ...
Two major kinds of lamins are present in vertebrate cells; the A and B types. The A-type lamins, lamins A and C, are ... code for the major B-type lamins (Gerace and Huber, 2012). At least one B-type lamin is thought to be expressed in all somatic ... 2012) B-type lamins and their elusive roles in metazoan cell proliferation and senescence. EMBO J 31:1058-1059, doi:10.1038/ ... We have studied a mouse model where Lamin B1 level are increased in oligodendrocytes, the cell type that produces myelin in the ...
Each type of cells displayed different proportionality of apoptosis. Mitochondrial DNA (mtDNA) copy number was dramatically ... Among them, lamin-A/C isoform 3 and PARP-1 were further confirmed using mRNA and protein expression study. Obvious ... Lamin-A/C isoform 3, talin-1, and annexin A1 were identified as universal biomarkers for PAHs exposure. Zebrafish, specifically ... The notable deregulated proteins for PAHs exposure were displayed as follows: lamin-A/C isoform 3 and annexin A1 for ...
Vertebrate lamins consist of two types, A and B. This gene encodes one of the two B type proteins, B1. Lamin B, along with ... Furukawa K, Kondo T (1998). "Identification of the lamina-associated-polypeptide-2-binding domain of B-type lamin". Eur. J. ... 1997). "A- and B-type lamins are differentially expressed in normal human tissues". Histochem. Cell Biol. 107 (6): 505-17. doi: ... During mitosis, the lamina matrix is reversibly disassembled as the lamin proteins are phosphorylated. Lamin proteins are ...
Felix Hartlepps lab contains the insert Lamin B1 and is published in Unpublished This plasmid is available through Addgene. ... Vector type. Mammalian Expression Growth in Bacteria. * Bacterial Resistance(s). Kanamycin * Growth Temperature ... pSpot-Tag-Lamin was a gift from Felix Hartlepp (Addgene plasmid # 117062 ; http://n2t.net/addgene:117062 ; RRID:Addgene_117062 ...
Tom Mistelis lab contains the insert lamin A and is published in Nat Med. 2005 Apr . 11(4):440-5. This plasmid is available ... Vector type. Mammalian Expression * Selectable markers. Neomycin (select with G418) Growth in Bacteria. * Bacterial Resistance( ... To generate the wt lamin A minigene, intron 11 was first introduced between exon 11 and exon 12 in the lamin A cDNA in pEGFP- ... To generate the minigene wt pEGFP-lamin Aintr11 was digested with EcoRI and BstWI enzymes to remove a region of lamin A cDNA ...
Knockout Tested Rabbit recombinant monoclonal Lamin B1 antibody [EPR22165-121] - BSA and Azide free. Validated in WB, IP, IHC, ... ab229025 was shown to specifically react with Lamin B1 in wild-type HAP1 cells as signal was lost in Lamin B1 knockout cells. ... All lanes : Anti-Lamin B1 antibody [EPR22165-121] (ab229025) at 1/1000 dilution. Lane 1 : Wild-type HAP1 cell lysate. Lane 2 : ... Lane 1 : Wild-type HAP1 whole cell lysate. Lane 2 : Lamin B1 knockout HAP1 whole cell lysate. Lane 3 : HepG2 (human ...
Lamin, facebook that event (god, did I just type that?) Wed. 11/14/12 8:25pm bennett4senate: @ngh yup, i mean, the production, ... Previous playlist , Back to Lamin playlists , Next playlist --, RSS feeds for Lamin: Playlists feed , MP3 archives feed ... E-mail Lamin Fofana , Other WFMU Playlists , All artists played by Lamin , Listen on the Internet , Contact Us , Music & ... Old Money & Lamin Fofana Ethiopia Ethiopia / Nāga Dutty Artz 1:47:53 (. ) ...
As with A-type lamins, there are multiple isoforms of B-type lamins, the most common being lamin B1 and lamin B2. They are ... and B-type lamins have found that the positions of introns/exons in B-type lamins have been conserved in A-type lamins, with ... This suggests that the common ancestor of these lamin types was a B-type lamin. Due to their properties as a type of IF protein ... of B-type lamins across multiple species have found evidence that supports that B-type lamins existed before A-type lamins. ...
  • The familial partial lipodystrophy of the Dunnigan type, one of the diseases due to mutations in the lamin A/C ( LMNA ) gene, is characterized by a lipodystrophic phenotype and shares some clinical and metabolic features with the type A syndrome. (diabetesjournals.org)
  • We linked this phenotype to a novel heterozygous missense mutation in the LMNA , predicting a G602S amino acid substitution in lamin A. This mutation cosegregated with impaired glucose tolerance, insulin resistance, and acanthosis nigricans in the absence of clinical lipodystrophy in the family. (diabetesjournals.org)
  • This study further extends the vast range of diseases linked to LMNA mutations and identifies another genetic cause for the type A insulin resistance syndrome. (diabetesjournals.org)
  • Mutations in lamins A and C, which are alternatively spliced products of the lamin A/C ( LMNA ) gene, are responsible for several genetic diseases, including familial partial lipodystrophy of the Dunnigan type (FPLD) ( 5 ). (diabetesjournals.org)
  • These common clinical and metabolic features of FPLD and type A insulin resistance syndrome led us to search for mutations of the LMNA gene in a patient with a typical type A phenotype. (diabetesjournals.org)
  • We linked this phenotype to a novel heterozygous missense mutation in the LMNA gene, predicting a G602S amino acid substitution in lamin A. Her skin fibroblasts exhibited nuclear alterations similar to those described in other laminopathies and showed several defects in the insulin transduction pathway. (diabetesjournals.org)
  • The A-type lamin knockout mouse (Lmna-/-) exhibits many characteristics of striated muscle laminopathies, such as muscular dystrophy, dilated cardiomyopathy and premature death at 6-8 weeks. (washington.edu)
  • In this dissertation, I use the Lmna-/- mouse model to further dissect and understand the role of lamin A in cardiac function, proposing some potential mechanisms that may be suitable for further investigation in human patients. (washington.edu)
  • Mutations in the LMNA gene, which encodes A-type lamins, or in the ZMPSTE24 gene, which encodes a zinc metalloprotease involved in the maturation of A-type lamins, are linked to a wide spectrum of tissue-specific and systemic diseases collectively called laminopathies. (uantwerpen.be)
  • Disease manifestations include muscular dystrophies, lipodystrophies, dilated cardiomyopathies and the premature aging syndromes Hutchinson-Gilford progeria (HGPS) and restrictive dermopathy (RD). To unveil A-type regulated pathways, we have optimized and used cellular models in which we blocked the expression of LMNA or ZMPSTE24. (uantwerpen.be)
  • and LMNA (encoding lamin A and C), responsible for autosomal dominant EDMD (AD-EDMD) and autosomal recessive EDMD (AR-EDMD). (elsevier.es)
  • In contrast, both overexpression of LMNA R482W in primary human preadipocytes and endogenous expression of A-type lamins R482W in FPLD2 patient fibroblasts, reduce A-type lamins-SREBP1 in situ interactions and upregulate a large number of SREBP1 target genes. (sigmaaldrich.com)
  • As this LMNA mutant was previously shown to inhibit adipogenic differentiation, we propose that deregulation of SREBP1 by mutated A-type lamins constitutes one underlying mechanism of the physiopathology of FPLD2. (sigmaaldrich.com)
  • The most crucial distinction is that B-type lamins, encoded by two human genes ( LMNB1 and LMNB2 ), are essential for viability of individual cells, whereas A-type lamins (encoded by LMNA ) are dispensable. (biologists.org)
  • The gene LMNA encodes the proteins lamins A and C and is implicated in nine different laminopathies - inherited diseases that are linked to premature ageing. (semanticscholar.org)
  • In humans, A-type lamins are encoded by the LMNA gene. (genetics.org)
  • This is a randomized, double-blind, placebo-controlled study in patients with dilated cardiomyopathy (DCM) due to a mutation of the gene encoding the lamin A/C protein (LMNA). (clinicaltrials.gov)
  • In the third step a region of pEGFP-lamin A containing the last 240 bp of exon 12 was amplified using the primers: LMNA-mini12F (5'-CAGAACTGCAGCATCATGTAATCTG-3')/ GFPvectorR. (addgene.org)
  • Expressed in differentiated cells, A-type lamins originate from the LMNA gene. (wikipedia.org)
  • These proteins are found in many different cell types in three different forms (A, B, and C). Lamins A and C are alternatively spliced versions of the LMNA gene. (thermofisher.com)
  • RATIONALE: Mutations in the LMNA gene, which encodes the nuclear lamina proteins lamin A and lamin C, are the most common cause of familial dilated cardiomyopathy (DCM). (garvan.org.au)
  • Sustained pressure overload generated by thoracic aortic constriction depressed ventricular contraction in young wild-type and Lmna(+/-) mice with no sex or genotype differences in the time-course or severity of response. (garvan.org.au)
  • Mutations in the LMNA gene, encoding the nuclear envelope protein lamin A/C, are responsible for a number of distinct disease entities including Dunnigan-type familial partial lipodystrophy. (cdc.gov)
  • Furthermore, several genome-wide linkage scans for type 2 diabetes have found evidence of linkage at chromosome 1q21.2, the region that harbors the LMNA gene. (cdc.gov)
  • Therefore, LMNA is a biological and positional candidate for type 2 diabetes susceptibility. (cdc.gov)
  • In the present study, we characterized the common variation across the LMNA gene (including rs4641) and tested for association with type 2 diabetes in two large case-control studies (n = 2,052) and with features of the metabolic syndrome in a separate cohort study (n = 1,572). (cdc.gov)
  • Despite our study being sufficiently powered to detect effects similar and even smaller in magnitude than those previously reported, none of the LMNA single nucleotide polymorphisms were statistically significantly associated with type 2 diabetes or the metabolic syndrome. (cdc.gov)
  • Thus, it appears unlikely that variation at LMNA substantially increases the risk of type 2 diabetes or related traits in U.K. Europids. (cdc.gov)
  • Adjusted OR of LMNA variants for type 2 diabetes incidence for the additive model. (cdc.gov)
  • Mutations in the LMNA gene, encoding A-type lamins, have been associated with at least 15 distinct diseases collectively termed laminopathies, including muscle, metabolic and neurological disorders, and premature aging syndrome. (uzh.ch)
  • LMNA also known as Lamin A/C is a major component of lamina, a thin proteinaceous filamentous meshwork that underlies the inner nuclear membrane. (novusbio.com)
  • Lamin A/C (LMNA) is located within a region on chromosome 1q that has been linked with Type II (non-insulin-dependent) diabetes mellitus in Pima Indians. (cdc.gov)
  • Rare mutations in exon 8 of LMNA underlie Dunnigan-Type familial partial lipodystrophy, a disease characterized by regional adipocyte degeneration and frequently accompanied by insulin resistance, glucose intolerance, and diabetes. (cdc.gov)
  • Because obesity is a strongly predisposing factor for Type II diabetes, we hypothesized that the LMNA 3408C/T variant could be associated with diabetes and body mass index in Pima Indians. (cdc.gov)
  • To determine whether the LMNA 3408C/T variant contributes to Type II diabetes susceptibility, we genotyped the polymorphism in 1,338 Pimas using allelic discrimination technology. (cdc.gov)
  • Furthermore, we showed that miR-761 putatively targeted three proteins, thyroid hormone receptor interactor 6 (TRIP6), lamin A/C (LMNA), and NAD-dependent protein deacetylase sirtuin-3 (SIRT3). (bireme.br)
  • The Biological Basis of Hutchinson-Gilford Syndrome (HGS): Relationship to Mutagens in the Lamin A/C Gene (LMNA) and to Other Known Laminopathies. (thefreedictionary.com)
  • The LMNA gene is found on chromosome 1q21.2-q21.3 in humans and encodes the lamin A/C proteins (Feng and Howard, 1993). (thefreedictionary.com)
  • Introduction Mutations in the lamin A/C gene (LMNA) cause an autosomal dominant inherited form of dilated cardiomyopathy (hereafter referred to as LMNA cardiomyopathy), often with concurrent muscular dystrophy (1,2). (deepdyve.com)
  • LMNA encodes the A-type nuclear lamins, which arise from alternative RNA splicing (3-5) and along with B-type lamins are the main constituents of nuclear lamina (6). (deepdyve.com)
  • LMNA encodes A-type lamins, intermediate filament proteins that form the nuclear lamina, a layer just under the nuclear membrane. (sciencemag.org)
  • Different LMNA mutations cause distinct diseases, but reduced A-type lamin function is generally linked to skeletal muscle dystrophy and dilated cardiomyopathy, in which the heart is enlarged and weakened. (sciencemag.org)
  • The LMNA gene codes for both lamin A and lamin C, but the mutation only affects the structure of lamin A because exon 11 of LMNA is not present in lamin C mRNA. (bmj.com)
  • The human LMNA gene encodes the essential nuclear envelope proteins lamin A and C (lamin A/C). Mutations in LMNA result in altered nuclear morphology, but how this impacts the mechanisms that maintain genomic stability is unclear. (asm.org)
  • Dunnigan-type familial partial lipodystrophy is a rare dominant autosomal disease resulting from a heterozygous missense mutation in the LMNA gene, known as LPF type 2 (Dunnigan variant), which encodes the nuclear protein A/C-type lamin. (scirp.org)
  • Lmna flox/flox mice possess loxP sites flanking exon 2 of the lamin A gene, making them useful for studying the role of Lamin-A in specific cell types, and its influence on the progression of human diseases. (jax.org)
  • Lmna flox/flox mutant mice possess loxP sites flanking exon 2 of the lamin A ( Lmna ) gene. (jax.org)
  • A targeting vector was designed to insert a loxP site upstream of exon 2, and a frt -flanked puromycin resistance (puro) cassette followed by a second loxP site, downstream of exon 2 of the lamin A ( Lmna ) gene. (jax.org)
  • Limb-girdle muscular dystrophy type 1B is caused by mutations (changes) to the LMNA gene. (malacards.org)
  • An important gene associated with Muscular Dystrophy, Limb-Girdle, Type 1b is LMNA (Lamin A/C), and among its related pathways/superpathways is Initiation of Nuclear Envelope Reformation . (malacards.org)
  • Particular forms of polycystic ovary syndrome with severe hyperandrogenism, acanthosis nigricans, and marked insulin resistance, defining the type A insulin resistance syndrome, are due to insulin receptor gene mutations. (diabetesjournals.org)
  • 1999 ). Mutations in the gene encoding lamin A/C cause autosomal dominant Emery-Dreifuss muscular dystrophy [In Process Citation]. (biologists.org)
  • Considered individually and collectively, partners for A-type lamins form four loose groups: architectural partners, chromatin partners, gene-regulatory partners and signaling partners. (biologists.org)
  • On the basis of our limited current knowledge, we propose lamin-associated complexes with multiple components relevant to nuclear structure (e.g. emerin, nesprin 1α, actin) or signaling and gene regulation (e.g. (biologists.org)
  • Using ablation of the unique lamin gene in C. elegans, we show that lamin is necessary for the perinuclear positioning of heterochromatin. (nih.gov)
  • Mutations in the human A-type lamin gene lead to diseases called laminopathies. (genetics.org)
  • Taken together, these data provide the first detailed genetic analysis of the LamC gene and support using Drosophila as a model to study the role of lamins in disease. (genetics.org)
  • Lamins are experiencing a growing interest, since a wide range of diseases are induced by mutations in the gene coding for A-type lamins, globally known as laminopathies. (mdpi.com)
  • Most of the DCM-related mutations fall in the Lamin AC gene, in particular in the Coil2B domain of the encoded protein. (rcsb.org)
  • In wild-type cells, expression of the mechanosensitive gene egr-1 and the anti-apoptotic gene iex-1 is rapidly up-regulated in response to mechanical stimulation (Sadoshima et al. (nih.gov)
  • Lamin-B1 is a protein that in humans is encoded by the LMNB1 gene. (wikipedia.org)
  • Lamin proteins are thought to be involved in nuclear stability, chromatin structure, and gene expression. (wikipedia.org)
  • Vertebrate lamins consist of two types, A and B. This gene encodes one of the two B type proteins, B1. (wikipedia.org)
  • Lamins have elastic and mechanosensitive properties, and can alter gene regulation in a feedback response to mechanical cues. (wikipedia.org)
  • Two isoforms, lamins A and C, can be created from this gene via alternative splicing. (wikipedia.org)
  • Analysis of the lamin A/C gene as a candidate for type II diabetes susceptibility in Pima Indians. (cdc.gov)
  • A-type lamins (A, A10, and C) are encoded by a single gene and are produced by alternative splicing, while B-type lamins (B1 and B2) are encoded by separate genes. (fishersci.com)
  • In addition to fulfilling structural functions at the nuclear envelope (NE), A-type lamins (lamin A and C) play important roles in the control of gene expression via their interaction with histones, transcription factors (e.g. (rupress.org)
  • This PA is a new initiative to support research to understand how mutations in the gene for lamin A/C affect nuclear structure, thus leading to bothdysfunction of the nuclear envelope, and depending on the mutation, Hutchinson-Gilford syndrome in humans (Eriksson et al. (thefreedictionary.com)
  • Vertebrate lamins consist of two types, A and B. Through alternate splicing, this gene encodes three type A lamin isoforms. (merckmillipore.com)
  • Charcot-Marie-Tooth disease type 1A (CMT1A) is caused by a uniform 1.5-Mb duplication on chromosome 17p, which includes the PMP22 gene. (iospress.com)
  • This gene encodes a type 2 integral membrane protein that binds A- and B-type lamins. (genecards.org)
  • It remains to be seen whether and how lamin B1-Oct-1 interactions are actively regulated in cells to help control gene expression. (phys.org)
  • Analyses of FISH signals in Arabidopsis lamin-like gene mutants. (biomedcentral.com)
  • Silences the Lamin A/C gene and is labeled with DY-547. (horizondiscovery.com)
  • Lamins A and C have close sequence homology and are derived by differential splicing and alternative polyadenylation from one gene. (horizondiscovery.com)
  • This gene provides instructions for making a protein called the lamin B receptor. (medlineplus.gov)
  • LBR gene mutations involved in Greenberg dysplasia lead to loss of the sterol reductase function of the lamin B receptor, and research suggests that this loss causes the condition. (medlineplus.gov)
  • Lamins are the main components of the nuclear lamina, a filamentous network located between inner nuclear membrane and chromatin that plays a fundamental role in nuclear organization in all differentiated cells ( 5 ). (diabetesjournals.org)
  • 1993 ). Lamin B distribution and association with peripheral chromatin revealed by optical sectioning and electron microscopy tomography. (biologists.org)
  • Nuclear lamins are involved in many cellular functions due to their ability to bind numerous partners including chromatin and transcription factors, and affect their properties. (sigmaaldrich.com)
  • Lamins are intermediate filaments that line the inner surface of the nuclear envelope, providing structural support and making contacts with chromatin. (genetics.org)
  • During this time period, investigations of rat liver nuclei revealed that lamins have an architectural relationship with chromatin and nuclear pores. (wikipedia.org)
  • For example, the lamins interact with chromatin in vitro and probably in vivo ( 2 , 16 , 22 , 47 ). (rupress.org)
  • For example, lamin B is associated with replicating chromatin in mammalian cells ( 39 ). (rupress.org)
  • Lamins are components of the nuclear lamina, a fibrous layer on the nucleoplasmic side of the inner nuclear membrane, which is thought to provide a framework for the nuclear envelope and may also interact with chromatin. (abcam.com)
  • Role of A-type lamins in signaling, transcription, and chromatin organization. (thefreedictionary.com)
  • Lamins, as well as providing support for the nuclear membrane , are involved in cell division, chromatin organization and DNA repair and more. (phys.org)
  • These findings suggest that a mutation in lamin A can affect insulin signaling and may be responsible for in vivo profound insulin resistance, leading to severe hyperandrogenism and oligomenorrhea but without significantly affecting adipose tissue distribution. (diabetesjournals.org)
  • 2000 ). Nuclear lamin A/C R482Q mutation in canadian kindreds with dunnigan-type familial partial lipodystrophy [In Process Citation]. (biologists.org)
  • OMIM#151660) is caused in most cases by the A-type lamin R482W mutation. (sigmaaldrich.com)
  • Lamin A/C mutation associated with lipodystrophy influences adipogenic differentiation of stem cells through interaction with Notch signaling. (semanticscholar.org)
  • We then express at low levels in otherwise wild-type worms a lamin carrying a point mutation, Y59C, which in humans is linked to an autosomal-dominant form of Emery-Dreifuss muscular dystrophy. (nih.gov)
  • A disease-linked point mutation in lamin impairs muscle-specific reorganization of a heterochromatic array during tissue-specific promoter activation in a dominant manner. (nih.gov)
  • Prominent interfamilial and intrafamilial variability can exist, even with the same mutation types. (medscape.com)
  • However, sometimes a clear difference between mutation types cannot be found in families. (medscape.com)
  • Fibroblasts from an individual with the E203K lamin A mutation also exhibit decreased lamin A sumoylation and increased cell death. (uky.edu)
  • Defects in nuclear structure and function promote dilated cardiomyopathy in lamin A/C-deficient mice. (semanticscholar.org)
  • Much of the current research on A-type lamins is focused on how mutations leading to alterations in these proteins cause dilated cardiomyopathy and other inherited diseases. (deepdyve.com)
  • We show that lamin A is sumoylated at lysine 201 and that two lamin A mutants associated with familial dilated cardiomyopathy, E203G and E203K, exhibit decreased sumoylation. (uky.edu)
  • 14, 15 Others include autosomal dominant (AD) and autosomal recessive (AR) Emery-Dreifuss muscular dystrophy type 2 (EDMD2), a form of AD dilated cardiomyopathy (CMD1A), AD Dunnigan-type familial partial lipodystrophy, AD limb girdle muscular dystrophy type 1B (LGMD1B), AR Charcot-Marie-Tooth disorder type 2B1 and AR mandibuloacral dysplasia (MAD). (bmj.com)
  • The following product was used in this experiment: Phospho-Lamin A/C (Ser22) Polyclonal Antibody from Thermo Fisher Scientific, catalog # PA5-97394, RRID AB_2809196. (thermofisher.com)
  • The following antibody was used in this experiment: Lamin B1 Monoclonal Antibody (L-5) from Thermo Fisher Scientific, catalog # 33-2000, RRID AB_2533106. (thermofisher.com)
  • Anti-Lamin A/C Antibody, clone 14 detects level of Lamin A/C & has been published & validated for use in IC & WB. (merckmillipore.com)
  • This antibody has been reported by an independent laboratory to detect Lamin A/C in human endothelial cells. (merckmillipore.com)
  • Alternative splicing generates messages encoding two isoforms: lamin A and lamin C. Expression of A-type lamins is limited to terminally differentiated somatic cells. (genetics.org)
  • Since different Lamin-A isoforms exist, this strain was developed to produce offspring that lack the majority of Lamin-A isoforms. (jax.org)
  • disorders associated with compromised A-type lamin function. (biologists.org)
  • Despite their clearly different roles, the conserved similarities between A- and B-type lamins suggest similar mechanisms of function in the nucleus. (biologists.org)
  • Lamins, also known as nuclear lamins are fibrous proteins in type V intermediate filaments, providing structural function and transcriptional regulation in the cell nucleus. (wikipedia.org)
  • Lamins were first identified in the cell nucleus, using electron-microscopy. (wikipedia.org)
  • These complex structures allow nuclear lamins to perform their specialized functions in maintaining the shape of the nucleus as well as roles during mitosis and apoptosis. (wikipedia.org)
  • The nuclear lamins have been associated with a number of processes in the nucleus, including DNA replication. (rupress.org)
  • In addition to providing mechanical support to the nucleus and influencing its shape and volume, the lamins appear to interact with other nuclear components and thereby may influence a number of nuclear processes ( 40 ). (rupress.org)
  • Lamins are the main component of the nuclear lamina, a protein meshwork at the inner nuclear membrane which primarily provide mechanical stability to the nucleus. (uzh.ch)
  • Protein phosphatase 1 (PP1), a Ser/Thr phosphatase, is the key enzyme responsible for dephosphorylation of lamins in the cell nucleus. (thefreedictionary.com)
  • We also previously demonstrated increased pERK1/2 primarily in the nucleus of transiently transfected C2C12 cells over-expressing the lamin A H222P variant (7). (deepdyve.com)
  • Computed reconstruction of the meshwork (magenta) created by the protein lamin B1 (red) on the inner surface of a mouse fibroblast nucleus. (phys.org)
  • Lamin helps sequester heterochromatin at the nuclear envelope, and wild-type lamin permits promoter release following tissue-specific activation. (nih.gov)
  • We also found that HECW2 interacts with wild-type lamin A and ubiquitinates it and this interaction is reduced in case of lamin mutants G232E and Q294P. (deepdyve.com)
  • When we examined protein extracts from stably transfected C2C12 cells expressing H222P lamin A (C2-H222P) at lower levels (24,25), we observed an increase in cytoplasmic relative to nuclear pERK1/2 compared with cells expressing wild-type lamin A (C2-WT) (Fig. 1B). (deepdyve.com)
  • Lamina-associated polypeptide (LAP)2, which directly interacts with B-type lamins and chromosomes, is an integral membrane protein specifically distributed along the inner nuclear membrane of the nuclear envelope. (nih.gov)
  • A-type lamins, primarily represented by the proteins lamin A and lamin C, are unique intermediate filaments that localize to the inner nuclear membrane to form the nuclear lamina. (washington.edu)
  • Lamins are type V intermediate filaments that collectively form a meshwork underneath the inner nuclear membrane, called nuclear lamina. (mdpi.com)
  • Nuclear lamins interact with inner nuclear membrane proteins to form the nuclear lamina on the interior of the nuclear envelope. (wikipedia.org)
  • Later in 1978, immunolabeling techniques revealed that lamins are localized at the nuclear envelope under the inner nuclear membrane. (wikipedia.org)
  • Lamins are intermediate filament proteins of the inner nuclear membrane required for the maintenance of nuclear structure and function. (semanticscholar.org)
  • The role of lamins has been studied from several perspectives, exploiting different techniques and procedures. (mdpi.com)
  • To further characterize the specific role of lamins in DNA replication, we have used a truncated human lamin as a dominant negative mutant to perturb lamin organization. (rupress.org)
  • These results could have implications for the role of lamins in other types of stem cell niches," Zheng said. (thefreedictionary.com)
  • Identification of the lamina-associated-polypeptide-2-binding domain of B-type lamin. (nih.gov)
  • 1999 ). Dynamics of the nuclear lamina as monitored by GFP-tagged A-type lamins. (biologists.org)
  • 1997 ). GST-lamin fusion proteins act as dominant negative mutants in Xenopus egg extract and reveal the function of the lamina in DNA replication. (biologists.org)
  • LamC aggregates also cause disorganization of lamin Dm 0 , indicating interdependence of both lamin types for proper lamina assembly. (genetics.org)
  • we can thus hypothesize that the mutations may interfere with the binding of components within the nuclear lamina, or of nuclear factors, that have been proposed to interact/associate with lamin A/C. (rcsb.org)
  • During mitosis, the lamina matrix is reversibly disassembled as the lamin proteins are phosphorylated. (wikipedia.org)
  • The major proteins comprising the lamina, the nuclear lamins, are also found in foci in the nucleoplasm, distinct from the peripheral lamina. (rupress.org)
  • In both cases, the lamina appears to be completely absent, and instead the endogenous lamins and the mutant lamin protein are found in nucleoplasmic aggregates. (rupress.org)
  • The nuclear lamin proteins form a fibrous structure, termed the nuclear lamina, which is concentrated at the nucleoplasmic face of the nuclear envelope ( 40 ). (rupress.org)
  • The chicken nuclear lamina is composed of at least three proteins called lamins A, B1 and B2. (unibas.ch)
  • The major component of nuclear lamina are intermediate filament-like proteins called lamins. (fishersci.com)
  • Parnaik, Veena K. 2018-08-01 00:00:00 Lamins constitute the major architectural proteins of the nuclear lamina that help in maintaining nuclear organization. (deepdyve.com)
  • Phosphorylation of nuclear lamin A/C by EBV-PK over serine residues 22, 390, and 392 promotes the disassembly of nuclear lamina ( 32 ), which could contribute to viral nuclear egress. (asm.org)
  • Lamin-A is part of the nuclear lamina seen in increasing levels of expression as development progresses. (jax.org)
  • Lamins are intermediate filament-type proteins, which form major components of the nuclear lamina. (horizondiscovery.com)
  • Drosophila possesses both lamin types, encoded by the LamC (A-type) and lamin Dm 0 (B-type) genes. (genetics.org)
  • In humans, B-type lamins are encoded by the genes LMNB1 and LMNB2 . (genetics.org)
  • a) Expression of the mechanosensitive genes iex-1 and egr-1 in response to mechanical strain is drastically reduced in emerin and A-type lamin-deficient fibroblasts compared with wild-type cells. (nih.gov)
  • 2002). To evaluate whether transcriptional activation for these genes was altered in A-type lamin or emerin-deficient cells, fibroblasts plated on fibronectin-coated silicone membranes were subjected to biaxial cyclic strain (4%, 1 Hz) and mRNA levels were subsequently analyzed using Northern analysis and real-time PCR. (nih.gov)
  • Mutations in lamin genes can result in several genetic laminopathies, which may be life-threatening. (wikipedia.org)
  • Studies of lamins became more popular in the 1990s when it was discovered that mutations in the genes that code for lamins can be related to muscular dystrophies, cardiomyopathies, and neuropathies. (wikipedia.org)
  • We used cDNA microarray to identify betulinic acid target genes and used tissue microarray to determine the expression levels of lamin B1 in pancreatic cancer tissues and to define their relationship with the clinicopathologic characteristics of pancreatic cancer. (aacrjournals.org)
  • The authors asked whether disrupting lamin B1-Oct-1 interactions could affect the expression of genes regulated by Oct-1. (phys.org)
  • Indeed, in cells with truncated lamin B1, they found that expression of several Oct-1-regulated genes was altered because more Oct-1 could bind at these genes' promoters. (phys.org)
  • A CaaX motif is found within the unique residues in prelamin A. Due to the presence of the CaaX motif, prelamin A undergoes a series of posttranslational modifications to become mature lamin A. These steps include farnesylation of the carboxyl-terminal cysteine, endoproteolytic release of the terminal amino acids, carboxymethalation of the accessible farnesylcysteine, and removal of the final fifteen residues by a zinc metalloprotease. (wikipedia.org)
  • However, whereas the lamin A precursor was stable, the translation product of the lamin B2 transcript was processed in the reticulocyte lysate to a polypeptide comigrating on two-dimensional gels with authentic mature lamin B2. (unibas.ch)
  • While they form in a TRF2-dependent manner similar to t-loops, ITLs further require the physical interaction of TRF2 with the nuclear intermediate filament protein lamin A/C. Our findings suggest that interactions between telomeres and the nucleoskeleton broadly impact genomic integrity, including telomere stability, chromosome structure, and chromosome fragility. (nih.gov)
  • By mass spectrometry of purified protein aggregates, a subset of spliceosomal components and nucleoskeletal protein lamin B1 were detected as constituent parts of an Hg-induced nuclear aggregome network. (peerj.com)
  • Furthermore, selective disruption of A-type lamin structures by overexpression of lamin mutants in HeLa cells caused a redistribution of LAP2alpha. (biologists.org)
  • We demonstrate that null mutations in LamC are lethal, and expression of a wild-type LamC transgene rescues lethality of LamC but not ttv mutants. (genetics.org)
  • In this context, we focussed our studies on the crystal structures of two lamin Coil2B domain mutants (R335W and E347K). (rcsb.org)
  • HECW2, a HECT-type E3 ubiquitin ligase, is transcriptionally upregulated in HeLa cells expressing Emery-Dreifuss muscular dystrophy-causing-lamin A mutants. (deepdyve.com)
  • Cells expressing lamin A mutants G232E and Q294P, in which HECW2 is upregulated, show increased proteasomal degradation of PCNA and lamin B1 most likely mediated by HECW2. (deepdyve.com)
  • Lamin A mutants E203G, E203K, and K201R all exhibit a similar aberrant subcellular localization and are associated with increased cell death. (uky.edu)
  • Using in situ proximity ligation assays (PLA), reporter assays and biochemical and transcriptomic approaches, we show that interactions of SREBP1 with lamin A and lamin C occur at the nuclear periphery and in the nucleoplasm. (sigmaaldrich.com)
  • In vitro studies have shown that dimers are the basic building blocks of higher order lamin structures and in low concentrations lamins are distributed throughout the nucleoplasm. (merckmillipore.com)
  • In humans, there are two types of lamins: A-type lamins (lamins A and C), found primarily in differentiated cells, and B-type lamins (lamins B1 and B2), found in all nucleated cells. (merckmillipore.com)
  • Our data provide direct, in vivo and in vitro evidence that the majority of type B lamins remain connected to nuclear membrane 'receptors' during mitosis. (nih.gov)
  • 1996 ). DNA from Drosophila melanogaster beta-heterochromatin binds specifically to nuclear lamins in vitro and the nuclear envelope in situ. (biologists.org)
  • Expression of a mutant lamin A that causes Emery-Dreifuss muscular dystrophy inhibits in vitro differentiation of C2C12 myoblasts. (semanticscholar.org)
  • A-type lamin-deficient cells have impaired mechanotransduction signaling in vivo and in vitro (Lammerding et al. (nih.gov)
  • This protein disrupts the lamin organization of nuclei when microinjected into mammalian cells and also disrupts the lamin organization of in vitro assembled nuclei when added to Xenopus laevis interphase egg extracts. (rupress.org)
  • Furthermore, we show that in vitro translation of transcripts derived from lamin A and lamin B2 cDNAs yielded polypeptides that were indistinguishable, by two-dimensional gel electrophoresis, from the putative in vivo precursors of lamins A and B2 respectively. (unibas.ch)
  • We describe here the case of a nonobese 24-year-old woman affected with type A syndrome without clinical lipodystrophy. (diabetesjournals.org)
  • The p.R482W substitution in A-type lamins deregulates SREBP1 activity in Dunnigan-type familial partial lipodystrophy. (sigmaaldrich.com)
  • With the possible exceptions of Dunnigan's familial partial lipodystrophy and HGPS, the amino acid substitutions responsible for a given laminopathy do not map to a specific domain of the lamin protein ( B urke and S tewart 2002 ). (genetics.org)
  • Dunningan-type lipodystrophy is characterized by loss of subcutaneous adipose tissue, insulin resistance, dyslipidemia, and type 2 diabetes and shares many of the features of the metabolic syndrome. (cdc.gov)
  • In addition, lamin A is mutated in lipodystrophy, a disorder characterized by reduction in subcutaneous adipose tissue. (fishersci.com)
  • Dunnigan-type partial lipodystrophy, which is characterized by a number of metabolic alterations, change in body fat distribution, and autosomal dominant inheritance pattern, is rare in the general population. (scirp.org)
  • Objective: To report the case of an adolescent with clinical and laboratory findings suggestive of Dunnigan-type partial lipodystrophy. (scirp.org)
  • Conclusion: This case report highlights the importance of suspecting Dunnigan-type familial partial lipodystrophy in clinical practice. (scirp.org)
  • Mutations in A-type lamins cause a bewildering range of tissue-specific diseases, termed `laminopathies', including Emery-Dreifuss muscular dystrophy and the devastating Hutchinson-Gilford progeria syndrome, which mimics premature aging. (biologists.org)
  • Emery-Dreifuss muscular dystrophy can be caused by mutations in the nuclear envelope proteins lamin A/C and emerin. (nih.gov)
  • The list includes 33 types of congenital muscular dystrophy, listed in alphabetical order. (mda.org)
  • Mice lacking lamin A show no overt abnormalities until postnatal development when perturbations in nuclear envelop structure correlate with the appearance of muscular dystrophy. (fishersci.com)
  • Mutations in lamins have been connected to more than a dozen human diseases, including muscular dystrophy, heart disease and progeria, a premature aging syndrome. (phys.org)
  • 53 Limb-girdle muscular dystrophy type 1B (LGMD1B) is one of many types of limb-girdle muscular dystrophy. (malacards.org)
  • Muscular Dystrophy, Limb-Girdle, Type 1b, also known as lgmd1b , is related to emery-dreifuss muscular dystrophy 2, autosomal dominant and emery-dreifuss muscular dystrophy . (malacards.org)
  • Mammalian cells encode both A-type and B-type lamins, which are highly related but can be distinguished biochemically and functionally. (biologists.org)
  • These transgenic animals display a nuclear lamin aggregation phenotype remarkably similar to that observed when human mutant A-type lamins are expressed in mammalian cells. (genetics.org)
  • Scientists at the A*STAR Institute of Medical Biology, led by Brian Burke, have constructed a nanoscale model of the inner side of the mammalian nuclear membrane , where threadlike proteins called lamins form a mesh. (phys.org)
  • They and additional partners bind `A-type' lamins, which form stable filaments in animal cell nuclei. (biologists.org)
  • B-type lamins are found in all nucleated somatic cells, while the expression of A-type lamins are developmentally regulated. (fishersci.com)
  • Type B lamins remain associated with the integral nuclear envelope protein p58 during mitosis: implications for nuclear reassembly. (nih.gov)
  • Using confocal microscopy and double immunolabelling, we show here that lamins B1 and B2 co-localize with p58 during all phases of mitosis and co-assemble around reforming nuclei. (nih.gov)
  • This sub-assembly does not include the type A lamins which are fully solubilized during mitosis. (nih.gov)
  • Unlike lamin B-binding LAP2beta, LAP2alpha was found by confocal immunofluorescence microscopy to colocalize preferentially with A-type lamins in the newly formed nuclei assembled after mitosis. (biologists.org)
  • Lamin proteins are involved in the disassembling and reforming of the nuclear envelope during mitosis, the positioning of nuclear pores, and programmed cell death. (wikipedia.org)
  • the phosphorylation of lamins is associated with mitosis and the breakdown of the nuclear envelope. (thefreedictionary.com)
  • Structural analysis of nuclei revealed that lamins form 3.5nm thick filaments often interact with nuclear pore complexes. (uzh.ch)
  • Recombinant fragment within Human Lamin B1 aa 450 to the C-terminus. (abcam.com)
  • Synthetic peptide corresponding to Human Lamin B1 aa 570-586 (C terminal). (abcam.com)
  • A-type lamins, although dispensable during development in mice, have key roles in differentiated tissues. (biologists.org)
  • As in previous studies (7,23), we demonstrated an increase in pERK1/2 in hearts of LmnaH222P/H222P mice compared with wild-type mice (Fig. 1A). (deepdyve.com)
  • To generate the wt lamin A minigene, intron 11 was first introduced between exon 11 and exon 12 in the lamin A cDNA in pEGFP-lamin A using a multi-step PCR reaction. (addgene.org)
  • To generate the minigene wt pEGFP-lamin Aintr11 was digested with EcoRI and BstWI enzymes to remove a region of lamin A cDNA from exon 1 to the first 91 bp of exon 9, filled with Klenow enzyme and self-ligated. (addgene.org)
  • These are divided into two types, A and B, based on criteria such as expression patterns and exon positions ( 53 ). (rupress.org)
  • 1997 ). Cell cycle changes in A-type lamin associations detected in human dermal fibroblasts using monoclonal antibodies. (biologists.org)
  • Interestingly, functional validation showed that loss of A- type lamins perturbed the coordination between focal adhesion formation and cytoskeletal tension. (uantwerpen.be)
  • In summary, we show that redox balance, focal adhesion and cytoskeletal tension are affected by loss of A-type lamins. (uantwerpen.be)
  • 1993 ). Internal lamin structures within G1nuclei of human dermal fibroblasts. (biologists.org)
  • Emerin-deficient mouse embryo fibroblasts have abnormal nuclear shape, but in contrast to A-type lamin-deficient cells, exhibit nuclear deformations comparable to wild-type cells in cellular strain experiments, and the integrity of emerin-deficient nuclear envelopes appeared normal in a nuclear microinjection assay. (nih.gov)
  • A subclass of developmentally regulated lamins having a neutral isoelectric point. (definitions.net)
  • Accumulation of mutant lamin A causes progressive changes in nuclear architecture in Hutchinson-Gilford progeria syndrome. (semanticscholar.org)
  • p58 (also referred to as the lamin B receptor) is an integral membrane protein of the nuclear envelope known to form a multimeric complex with the lamins and other nuclear proteins during interphase. (nih.gov)
  • Lamin B, along with heterochromatin, is anchored to the inner surface of the nuclear membrane by the lamin B receptor. (wikipedia.org)
  • During cholesterol synthesis, the sterol reductase function of the lamin B receptor allows the protein to perform one of several steps that convert a molecule called lanosterol to cholesterol. (medlineplus.gov)
  • Silve S, Dupuy PH, Ferrara P, Loison G. Human lamin B receptor exhibits sterol C14-reductase activity in Saccharomyces cerevisiae. (medlineplus.gov)
  • Coincident with the disruption of lamin organization, there is a dramatic reduction in DNA replication. (rupress.org)
  • Using an advanced array of techniques available in fruit fly studies, the team demonstrated that lamins were a necessary component of supporting niche organization, which in turn regulates proper proliferation and differentiation of germline stem cells in fruit fly testis. (thefreedictionary.com)
  • Their findings may explain how even subtle changes in nuclear lamin organization can give rise to a bewildering array of human diseases. (phys.org)
  • Moreover, hindering ERK1/2-dependent phosphorylation of c-Fos attenuates its release from the ERNF induced by serum and promotes its interaction with lamin A. Accordingly, serum stimulation rapidly releases preexisting c-Fos from the NE via ERK1/2-dependent phosphorylation, leading to a fast activation of AP-1 before de novo c-Fos synthesis. (rupress.org)
  • Moreover, lamin A-null cells exhibit increased AP-1 activity and reduced levels of c-Fos phosphorylation. (rupress.org)
  • Thus, NE-bound ERK1/2 functions as a molecular switch for rapid mitogen-dependent AP-1 activation through phosphorylation-induced release of preexisting c-Fos from its inhibitory interaction with lamin A/C. (rupress.org)
  • Therein, mitogen-induced ERK1/2-mediated phosphorylation of c-Fos releases it from the inhibitory interaction with lamin A/C before de novo synthesis of c-Fos, thus allowing a rapid induction of AP-1 activity. (rupress.org)
  • B-type lamins undergo a series of modifications, such as farnesylation and phosphorylation. (abcam.com)
  • Increased phosphorylation of the lamins occurs before envelope disintegration and probably plays a role in regulating lamin associations. (abcam.com)
  • We show that 293T cells have a much higher level of constitutive lamin A/C phosphorylation than do 293 cells over residues (S22 and S392) that promote phosphorylation-dependent nuclear disassembly and that both large T and small t contribute to enhanced lamin A/C phosphorylation. (asm.org)
  • These results suggest that essential roles of EBV-PK during lytic viral replication include the phosphorylation and dispersion of lamin A/C. (asm.org)
  • Coimmunoprecipitation experiments revealed that a fraction of lamin A/C formed a stable, SDS-resistant complex with LAP2alpha in interphase cells and in postmetaphase cell extracts. (biologists.org)
  • Recent evidence has demonstrated that lamins A and C have essential functions in protecting cells from physical damage, as well as in maintaining the function of transcription factors required for the differentiation of adult stem cells. (semanticscholar.org)
  • Adult stem cell maintenance and tissue regeneration in the ageing context: the role for A-type lamins as intrinsic modulators of ageing in adult stem cells and their niches. (semanticscholar.org)
  • We recently demonstrated that A-type lamin-deficient cells have impaired nuclear mechanics and altered mechanotransduction, suggesting two potential disease mechanisms (Lammerding, J., P.C. Schulze, T. Takahashi, S. Kozlov, T. Sullivan, R.D. Kamm, C.L. Stewart, and R.T. Lee. (nih.gov)
  • The elevated baseline expression of iex-1 and egr-1 seen in the emerin-deficient cells in this Northern blot are not representative, and real-time PCR analysis didn't reveal any significant differences in baseline expression between cell types. (nih.gov)
  • b) Real-time PCR analysis confirms the impaired induction of iex-1 in response to strain in emerin and A-type lamin-deficient cells. (nih.gov)
  • 2004), and insufficient anti-apoptotic signaling could provide one explanation for the increased apoptotic cell fractions in A-type lamin and emerin-deficient cells seen in the 24-h strain experiments. (nih.gov)
  • Each type of cells displayed different proportionality of apoptosis. (hindawi.com)
  • B-type lamins are expressed in all cells, while the A-type lamins are expressed in differentiated cells ( 40 ). (rupress.org)
  • We first examined by Western blot the consequences of altering lamin A/C expression on the amount of c-Fos within the soluble nuclear fraction (SNF) and extraction-resistant nuclear fraction (ERNF) of cultured cells. (rupress.org)
  • However, the role of HECW2 upregulation in mediating downstream effects in lamin mutant-expressing cells was previously unexplored. (deepdyve.com)
  • Our findings establish HECW2 as an E3 ubiquitin ligase for PCNA and lamin B1 which regulates their levels in laminopathic cells. (deepdyve.com)
  • Finally, we demonstrate that knockdown of lamin A/C expression using small interfering RNA also rescues the PKmut phenotype in 293 cells. (asm.org)
  • Mouse B-type lamins are required for proper organogenesis but not by embryonic stem cells. (thefreedictionary.com)
  • Here, we report that lamin A/C-deficient cells have a normal response to ionizing radiation but are sensitive to agents that cause interstrand cross-links (ICLs) or replication stress. (asm.org)
  • In response to treatment with ICL agents (cisplatin, camptothecin, and mitomycin), lamin A/C-deficient cells displayed normal γ-H2AX focus formation but a higher frequency of cells with delayed γ-H2AX removal, decreased recruitment of the FANCD2 repair factor, and a higher frequency of chromosome aberrations. (asm.org)
  • Similarly, following hydroxyurea-induced replication stress, lamin A/C-deficient cells had an increased frequency of cells with delayed disappearance of γ-H2AX foci and defective repair factor recruitment (Mre11, CtIP, Rad51, RPA, and FANCD2). (asm.org)
  • Taken together, the data can be interpreted to suggest that lamin A/C has a role in the restart of stalled replication forks, a prerequisite for initiation of DNA damage repair by the homologous recombination pathway, which is intact in lamin A/C-deficient cells. (asm.org)
  • show-in the January 12, 2009 issue of the Journal of Cell Biology ( www.jcb.org )-that Oct-1 binds to lamin B1, a prominent intermediate filament that lines the nuclear envelope, and in cells expressing a drastically truncated mutant of lamin B1, Oct-1 was disassociated from the nuclear envelope. (phys.org)
  • As a result, these mutant cells accumulated higher levels of reactive oxygen species than wild-type cells. (phys.org)
  • But, it is evident from these results that perturbation of lamin B1-Oct-1 interactions can make cells more vulnerable to oxidative stress. (phys.org)
  • This could be particularly important in aging cells, where nuclear envelope integrity (and lamin B1 localization) is often perturbed, says author David Vaux. (phys.org)
  • Increased production of reactive oxygen species-due to the perturbation of lamin B1 in mature cells-could be another way in which lamins contribute to the aging process. (phys.org)
  • siGLO Lamin A/C Control siRNA is a validated positive control, guaranteed to silence Lamin A/C in human cells. (horizondiscovery.com)
  • Sustained knockdown revealed that both persistent prelamin A accumulation and lamin A/C depletion elevated intracellular ROS levels, but to a different extent, and with different effects on cell fate. (uantwerpen.be)
  • Lamin Bl depletion from the honeycombs was accompanied by depletion of nuclear pore complexes. (inforoku.com)
  • The depletion of PIP2 by type I PIP kinase (PPK-1) kinase RNA interference results in an altered chromosome structure and leads to various defects during meiotic progression. (mdpi.com)
  • Lamin A/C regulates nuclear shape/rigidity and provides a scaffold-type support for chromosomes or replicating DNA to interact with epigenetic machinery. (novusbio.com)
  • Point mutations in lamin A have been implicated in a wide variety of human diseases, termed laminopathies, which are categorized roughly into those affecting striated muscle tissue function, adipose tissue distribution, or pathologies associated with rapid aging in multiple tissues. (washington.edu)
  • Nuclear lamins, diseases and aging. (semanticscholar.org)
  • A-type lamin complexes and regenerative potential: a step towards understanding laminopathic diseases? (semanticscholar.org)
  • Mutations in lamins are associated with diverse degenerative diseases, collectively termed laminopathies. (deepdyve.com)
  • Lamin A mutations cause many diseases, including cardiomyopathies and Progeria Syndrome. (uky.edu)
  • We found that amino acids in the region of residues 78-258 of the lamin B1 rod domain directly bound with LAP2. (nih.gov)
  • Furthermore, lamin C contains six unique amino-acid residues while prelamin A contains ninety-eight residues not found in the other isoform. (wikipedia.org)
  • steroids for women A type lamins and their associated protein emerin co localized in these structures. (inforoku.com)
  • Lamin precursors processing is discussed in relation to characteristic differences in the interactions of A and B-type lamins with the nuclear membrane. (unibas.ch)
  • For example, the A-type lamin, LaC, binds to a protein that is part of the channels surrounding the holes on the nuclear membrane. (phys.org)
  • Here, we review the roles of TRF2 and lamin A/C in telomere biology and consider how their interaction may relate telomere homeostasis to cellular and organismal aging. (nih.gov)
  • Through this interaction, the lamins may be involved in DNA replication. (rupress.org)
  • Interaction with lamins B1 and C is hardly detectable (By similarity). (rcsb.org)
  • Sequestration of c-Fos at the nuclear envelope (NE) through interaction with A-type lamins suppresses AP-1-dependent transcription. (rupress.org)
  • We show here that c-Fos accumulation within the extraction-resistant nuclear fraction (ERNF) and its interaction with lamin A are reduced and enhanced by gain-of and loss-of ERK1/2 activity, respectively. (rupress.org)
  • Here we tested the hypothesis that ERK1/2 is a critical regulator of the interaction between lamin A/C and c-Fos. (rupress.org)
  • These findings open up new treatment strategies for laminopathies, in particular for muscular dystrophies, dilated cardiomyopathies and mandibuloacral dysplasia type B. These treatments strategies include reducing ROS levels, restoring mitochondrial function, increasing proteasome activity and increasing autophagy. (uantwerpen.be)
  • Current research is being performed to develop treatment methods for the aforementioned laminopathies and to investigate the role lamins play in the aging process. (wikipedia.org)
  • Our findings suggest that interplay among HECW2, lamin A, PCNA, and lamin B1 determines their respective homeostatic levels in the cell and dysregulation of these interactions may contribute to the pathogenicity of laminopathies. (deepdyve.com)
  • In this study to further define its role, we examined which domain of B-type lamin interacts with LAP2 by means of a binding assay with bacterially expressed proteins and a yeast two-hybrid system. (nih.gov)
  • Interacts with A-type lamin. (rcsb.org)
  • We also find that active ERK1/2 interacts with lamin A and colocalizes with c-Fos and A-type lamins at the NE. (rupress.org)
  • We show that active ERK1/2 directly interacts with lamin A and colocalizes with c-Fos at the NE. (rupress.org)
  • Here, we show that HECW2 interacts with two lamin A-binding proteins, proliferating cell nuclear antigen (PCNA), via a canonical PCNA-interacting protein (PIP) motif, and lamin B1. (deepdyve.com)
  • Mechanical stress-induced apoptosis has been proposed as the mechanism underpinning DCM in lamin A/C-deficient hearts, but supporting in vivo evidence has been lacking. (garvan.org.au)
  • CONCLUSIONS: These data suggest that factors other than mechanical stress-induced apoptosis contribute to DCM and provide the first demonstration that regular moderate exercise and carvedilol can modify disease progression in lamin A/C-deficient hearts. (garvan.org.au)
  • It is not a target for ced-3 during apoptosis, suggesting that lamin cleavage is not essential for apoptosis in C.elegans. (antibodies-online.com)
  • Nuclear lamins are involved in a number of essential nuclear functions, including nuclear envelope assembly and disassembly during cell division, DNA synthesis, transcription, and apoptosis. (merckmillipore.com)
  • Like other intermediate filament proteins, lamins consist of an N-terminal head domain, a central coiled-coil (rod) domain responsible for dimerization, and a large globular C-terminal tail. (biologists.org)
  • Similar to other IF proteins, lamins self-assemble into more complex structures. (wikipedia.org)
  • A-type lamins are characterized by a neutral isoelectric point, and they are typically displayed during later stages of embryonic development. (wikipedia.org)
  • Lamins are a class of intermediate filament proteins that form a matrix on the inner surface of the nuclear envelope. (thermofisher.com)
  • We describe 16 partners in detail, summarize their binding sites in A-type lamins, and sketch portraits of ternary complexes and functional pathways that might depend on lamins in vivo. (biologists.org)