Lamin Type A: A subclass of developmentally regulated lamins having a neutral isoelectric point. They are found to disassociate from nuclear membranes during mitosis.Lamin Type B: A subclass of ubiquitously-expressed lamins having an acidic isoelectric point. They are found to remain bound to nuclear membranes during mitosis.Lamins: Nuclear matrix proteins that are structural components of the NUCLEAR LAMINA. They are found in most multicellular organisms.Nuclear Lamina: A lattice of fibrils which covers the entire inner surface of the nuclear envelope and interlinks nuclear pores (NUCLEAR PORE).Nuclear Envelope: 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).Progeria: 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.Thymopoietins: 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.Muscular Dystrophy, Emery-Dreifuss: 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.Nuclear Proteins: 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.Cell 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)Lipodystrophy: 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.Lipodystrophy, Familial Partial: 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.Aging, Premature: Changes in the organism associated with senescence, occurring at an accelerated rate.Nuclear Matrix: 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)Protein Prenylation: 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.Caspase 6: 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.Cell Nucleus Shape: The quality of surface form or outline of the CELL NUCLEUS.Oligomenorrhea: Abnormally infrequent menstruation.Reunion: 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)Ethynodiol Diacetate: A synthetic progestational hormone used alone or in combination with estrogens as an oral contraceptive.Puberty, Precocious: 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.Hirsutism: 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.Adrenarche: 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.Hair: 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.Encyclopedias as Topic: 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)Nuclear Pore: 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.Mechanotransduction, Cellular: 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.Immediate-Early Proteins: 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.Apoptosis Regulatory Proteins: 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.Azides: Organic or inorganic compounds that contain the -N3 group.Antibodies, Monoclonal: Antibodies produced by a single clone of cells.Influenzavirus A: 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.Sodium Azide: A cytochrome oxidase inhibitor which is a nitridizing agent and an inhibitor of terminal oxidation. (From Merck Index, 12th ed)Antibodies: 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).Music: Sound that expresses emotion through rhythm, melody, and harmony.Nurse Midwives: Professional nurses who have received postgraduate training in midwifery.Music Therapy: The use of music as an adjunctive therapy in the treatment of neurological, mental, or behavioral disorders.Head: 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.Stress, Mechanical: A purely physical condition which exists within any material because of strain or deformation by external forces or by non-uniform thermal expansion; expressed quantitatively in units of force per unit area.Carbazoles: Benzo-indoles similar to CARBOLINES which are pyrido-indoles. In plants, carbazoles are derived from indole and form some of the INDOLE ALKALOIDS.Propanolamines: AMINO ALCOHOLS containing the propanolamine (NH2CH2CHOHCH2) group and its derivatives.Antibody Specificity: The property of antibodies which enables them to react with some ANTIGENIC DETERMINANTS and not with others. Specificity is dependent on chemical composition, physical forces, and molecular structure at the binding site.Antibodies, Viral: Immunoglobulins produced in response to VIRAL ANTIGENS.Solar System: The group of celestial bodies, including the EARTH, orbiting around and gravitationally bound by the sun. It includes eight planets, one minor planet, and 34 natural satellites, more than 1,000 observed comets, and thousands of lesser bodies known as MINOR PLANETS (asteroids) and METEOROIDS. (From Academic American Encyclopedia, 1983)Planets: Celestial bodies orbiting around the sun or other stars.Trinitrobenzenesulfonic Acid: A reagent that is used to neutralize peptide terminal amino groups.Steroids: A group of polycyclic compounds closely related biochemically to TERPENES. They include cholesterol, numerous hormones, precursors of certain vitamins, bile acids, alcohols (STEROLS), and certain natural drugs and poisons. Steroids have a common nucleus, a fused, reduced 17-carbon atom ring system, cyclopentanoperhydrophenanthrene. Most steroids also have two methyl groups and an aliphatic side-chain attached to the nucleus. (From Hawley's Condensed Chemical Dictionary, 11th ed)Cellular Phone: Analog or digital communications device in which the user has a wireless connection from a telephone to a nearby transmitter. It is termed cellular because the service area is divided into multiple "cells." As the user moves from one cell area to another, the call is transferred to the local transmitter.Wind: The motion of air relative to the earth's surface.Databases, Protein: Databases containing information about PROTEINS such as AMINO ACID SEQUENCE; PROTEIN CONFORMATION; and other properties.Internet: A loose confederation of computer communication networks around the world. The networks that make up the Internet are connected through several backbone networks. The Internet grew out of the US Government ARPAnet project and was designed to facilitate information exchange.User-Computer Interface: The portion of an interactive computer program that issues messages to and receives commands from a user.Software: Sequential operating programs and data which instruct the functioning of a digital computer.Proteins: Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.Sequence Analysis, Protein: A process that includes the determination of AMINO ACID SEQUENCE of a protein (or peptide, oligopeptide or peptide fragment) and the information analysis of the sequence.Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories for solving biological problems including manipulation of models and datasets.

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)

  • Taken together, our data suggest that both persistent prelamin A accumulation and lamin A/C depletion elevate ROS levels, but to a different extent and with different effects on cell fate. (ru.nl)
  • 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)
  • Despite their clearly different roles, the conserved similarities between A- and B-type lamins suggest similar mechanisms of function in the nucleus. (biologists.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)
  • 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)
  • 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)
  • Together, these data suggest that hypophosphorylated Rb is anchored in the nucleus by the interaction of pocket C with LAP2-lamin A/C complexes. (dur.ac.uk)
  • A meshwork formed by four nuclear lamins (lamins A, C, B1 and B2) long has been recognized to provide structural support for the cell nucleus. (asbmb.org)
  • Young and co-workers proposed that the ability to move the cell nucleus is impaired by the loss of either lamin B1 or lamin B2, resulting in defective migration of neurons. (asbmb.org)
  • Nuclear lamin‐A represses cell locomotion by stiffening the nucleus. (els.net)
  • 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)
  • Mutations in lamin genes can result in laminopathies, some of which are potentially lethal disorders. (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)
  • 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)
  • 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)
  • B type lamins, B1 and B2, are expressed from the LMNB1 and LMNB2 genes on 5q23 and 19q13, respectively. (lsbio.com)
  • We have also performed RNA-seq analysis in wild type, emr-1 and lem-2 mutants to correlate the NE association of genes with their transcriptional status. (csic.es)
  • 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)
  • 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)
  • 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)
  • Lamin A mutants E203G, E203K, and K201R all exhibit a similar aberrant subcellular localization and are associated with increased cell death. (uky.edu)
  • On redistribution of endogenous lamin A/C and LAP2 into nuclear aggregates by overexpressing dominant negative lamin mutants in tissue culture cells, Rb was also sequestered into these aggregates. (dur.ac.uk)
  • Emery-Dreifuss muscular dystrophy can be caused by mutations in the nuclear envelope proteins lamin A/C and emerin. (nih.gov)
  • 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)
  • 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)
  • Both emerin and lamin C depend on lamin A for localization at the nuclear envelope. (dur.ac.uk)
  • Vaughan, O. A. and Alvarez-Reyes, M. and Bridger, J. M. and Broers, J. L. V. and Ramaekers, F. C. S. and Wehnert, M. and Morris, G. E. and Whitfield, W. G. F. and Hutchison, C. J. (2001) 'Both emerin and lamin C depend on lamin A for localization at the nuclear envelope. (dur.ac.uk)
  • In two cell lines that did not express lamin A but did express lamin C, lamin C as well as emerin was mis-localised. (dur.ac.uk)
  • We have created C. elegans strains containing single copy insertions of Dam fused to two NE proteins, lamin/LMN-1 and emerin/EMR-1. (csic.es)
  • 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)
  • The very first modification involving farnesylation of prelamin A is crucial to the development of mature lamin A. Isoform lamin C does not undergo posttranslational modifications. (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)
  • Our data demonstrate that the Ig-fold motif located in the lamin C terminus binds directly to proliferating cell nuclear antigen (PCNA), the processivity factor necessary for the chain elongation phase of DNA replication. (rupress.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)
  • 1997 ). Cell cycle changes in A-type lamin associations detected in human dermal fibroblasts using monoclonal antibodies. (biologists.org)
  • Test your therapeutic antibodies in immunohistochemistry against a broad panel of normal frozen human tissue types in order to determine potential unintended binding. (lsbio.com)
  • 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)
  • Mammalian cells encode both A-type and B-type lamins, which are highly related but can be distinguished biochemically and functionally. (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)
  • 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)
  • Each type of cells displayed different proportionality of apoptosis. (hindawi.com)
  • 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)
  • B-type lamins are found in all nucleated somatic cells, while the expression of A-type lamins are developmentally regulated. (fishersci.com)
  • Moreover, lamin A-null cells exhibit increased AP-1 activity and reduced levels of c-Fos phosphorylation. (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)
  • 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)
  • 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)
  • 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)
  • B-type lamins are expressed in all cells, while the A-type lamins are expressed in differentiated cells ( 40 ). (rupress.org)
  • 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)
  • 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)
  • 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)
  • 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)
  • In animal cells, there are A- and B-type lamins, which differ in their length and isoelectric point (pI). (lsbio.com)
  • Finally, lamins A and C were selectively eliminated from the NE of HeLa cells using a dominant negative mutant of lamin B1. (dur.ac.uk)
  • Mechanistic studies revealed that the exon 11 sequences contain binding sites for serine/arginine-rich splicing factor 2 (SRSF2), and SRSF2 knockdown lowered lamin A production in cells and in murine tissues. (jci.org)
  • A ) siRNA knockdown of SRSF2 increases lamin C levels in human cells. (jci.org)
  • Earlier studies had proposed that the B-type lamins (lamins B1 and B2) play unique and important roles in DNA replication and cell division, but the studies by Young and Fong showed that a complete absence of both lamin B1 and lamin B2 in skin cells or liver cells has no adverse consequences. (asbmb.org)
  • While Lamin B is expressed in all nucleated cells studied, Lamin A/C are transcribed in most somatic cell types except mature B lymphocytes. (preprints.org)
  • Comparison of lamin B2 with lamins A and B1 in the accompanying paper provides definitive proof for the existence of two structurally distinct chicken B-type lamins. (unibas.ch)
  • They speculated that certain neurodevelopmental abnormalities in humans ultimately will be linked to genetic defects in lamin B1 or lamin B2. (asbmb.org)
  • Lamins, classified as A- or B-types on the basis of biochemical properties, have a conserved globular head, central rod and C-terminal domain that includes an Ig-fold structural motif. (umassmed.edu)
  • As a consequence of this disruption, the distributions of PCNA and the large subunit of the RFC complex, proteins required for the elongation phase of DNA replication, are altered such that they are found within the intranucleoplasmic lamin aggregates. (rupress.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)
  • 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 the current study, we sought to determine the role and regulation of lamin B1 expression in human pancreatic cancer pathogenesis and betulinic acid-based therapy. (aacrjournals.org)
  • 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)
  • 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)
  • 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)
  • 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)
  • Here we tested the hypothesis that ERK1/2 is a critical regulator of the interaction between lamin A/C and c-Fos. (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)
  • 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)
  • 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)
  • 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)
  • 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)
  • Unlike lamin C, Lamin A is generated in a precursor form called prelamin A. Prelamin A and lamin C differ in structure only at the carboxyl-terminus. (wikipedia.org)
  • Here, prelamin A contains two extra exons that lamin C lacks. (wikipedia.org)
  • T). The reporter yields 3 transcripts (glo-prelamin A, glo-lamin C, and glo-progerin). (jci.org)
  • After 2 days, glo-prelamin A, glo-progerin, and glo-lamin C transcripts were quantified by qRT-PCR and normalized to levels of the glo-only transcript. (jci.org)