Genomes and Genes
lamin type a
Summary: A subclass of developmentally regulated lamins having a neutral isoelectric point. They are found to disassociate from nuclear membranes during mitosis.
- Qin Z, Kalinowski A, Dahl K, Buehler M. Structure and stability of the lamin A tail domain and HGPS mutant. J Struct Biol. 2011;175:425-33 pubmed publisher..Also, this study provides the first molecular structure(s) of the lamin A tail domain, which is confirmed by thermodynamic tests in experiment. ..
- Kolb T, Maass K, Hergt M, Aebi U, Herrmann H. Lamin A and lamin C form homodimers and coexist in higher complex forms both in the nucleoplasmic fraction and in the lamina of cultured human cells. Nucleus. 2011;2:425-33 pubmed publisher..Hence, the structural segregation of lamin A and C is indeed retained in the nuclear envelope to some extent too. ..
- Harper M, Tillit J, Kress M, Ernoult Lange M. Phosphorylation-dependent binding of human transcription factor MOK2 to lamin A/C. FEBS J. 2009;276:3137-47 pubmed publisher..These three serine residues are located in the lamin A/C-binding domain. Interestingly, we were able to demonstrate that the phosphorylation of hsMOK2 interfered with its ability to bind lamin A/C. ..
- Conneely K, Capell B, Erdos M, Sebastiani P, Solovieff N, Swift A, et al. Human longevity and common variations in the LMNA gene: a meta-analysis. Aging Cell. 2012;11:475-81 pubmed publisher..18, P=7.5 × 10(-4) , multiple-testing-adjusted P=0.037). These results suggest that LMNA variants may play a role in human lifespan. ..
- Kong L, Schafer G, Bu H, Zhang Y, Zhang Y, Klocker H. Lamin A/C protein is overexpressed in tissue-invading prostate cancer and promotes prostate cancer cell growth, migration and invasion through the PI3K/AKT/PTEN pathway. Carcinogenesis. 2012;33:751-9 pubmed publisher..Together, our data suggest that lamin A/C proteins are positively involved in malignant behavior of PC cells through the PI3K/AKT/PTEN pathway. Lamin A/C may represent a new oncogenic factor and a novel therapeutic target for PC. ..
- Decker M, Chavez E, Vulto I, Lansdorp P. Telomere length in Hutchinson-Gilford progeria syndrome. Mech Ageing Dev. 2009;130:377-83 pubmed publisher..Our results suggest that mutant lamin A decreases telomere length via a direct effect and that expression of mutant LMNA is necessary for telomere loss in HGPS. ..
- Kubben N, Voncken J, Konings G, van Weeghel M, van den Hoogenhof M, Gijbels M, et al. Post-natal myogenic and adipogenic developmental: defects and metabolic impairment upon loss of A-type lamins. Nucleus. 2011;2:195-207 pubmed publisher..Our results indicate that defective early post-natal development critically contributes to the disease phenotypes in adult laminopathies. ..
- Borrego Pinto J, Jegou T, Osorio D, Aurade F, Gorjanacz M, Koch B, et al. Samp1 is a component of TAN lines and is required for nuclear movement. J Cell Sci. 2012;125:1099-105 pubmed publisher..These results support a role for Samp1 in the association between the LINC complex and lamins during nuclear movement. ..
- Meinke P, Nguyen T, Wehnert M. The LINC complex and human disease. Biochem Soc Trans. 2011;39:1693-7 pubmed publisher..Thus the association of LINC with human disease provides tools for understanding its functions within the cell. ..
- Duque G, Li W, Yeo L, Vidal C, Fatkin D. Attenuated anabolic response to exercise in lamin A/C haploinsufficient mice. Bone. 2011;49:412-8 pubmed publisher..In summary, our data indicate that the presence of lamin A/C is required for the anabolic effect of exercise on bone thus suggesting a new important role of lamin A/C in bone biology. ..
- Boudreau E, Labib S, Bertrand A, Decostre V, Bolongo P, Sylvius N, et al. Lamin A/C mutants disturb sumo1 localization and sumoylation in vitro and in vivo. PLoS ONE. 2012;7:e45918 pubmed publisher..However, lamin A and C did not appear to be modified by sumo1. Our results suggest that mutant lamin A/C alters the dynamics of sumo1 and thus misregulation of sumoylation may be contributing to disease progression in laminopathies. ..
- Goudenege S, LeBel C, Huot N, Dufour C, Fujii I, Gekas J, et al. Myoblasts derived from normal hESCs and dystrophic hiPSCs efficiently fuse with existing muscle fibers following transplantation. Mol Ther. 2012;20:2153-67 pubmed publisher..Our findings provide an effective method that will permit to use hESCs or hiPSCs for preclinical studies in muscle repair. ..
- Gonzalez Suarez I, Redwood A, Gonzalo S. Loss of A-type lamins and genomic instability. Cell Cycle. 2009;8:3860-5 pubmed..These studies support the notion that increased genomic instability due to defects in telomere biology and DNA repair contribute to the pathogenesis of lamin-related diseases. ..
- Akasaka H, Katsuya T, Saitoh S, Sugimoto K, Ohnishi H, Congrains A, et al. A promoter polymorphism of lamin A/C gene is an independent genetic predisposition to arterial stiffness in a Japanese general population (the Tanno and Sobetsu study). J Atheroscler Thromb. 2009;16:404-9 pubmed..Promoter -1030C/T polymorphism of LMNA is a possible genetic predisposition to arterial stiffness in the Japanese population. ..
- Redwood A, Perkins S, VanderWaal R, Feng Z, Biehl K, Gonzalez Suarez I, et al. A dual role for A-type lamins in DNA double-strand break repair. Cell Cycle. 2011;10:2549-60 pubmed..In addition, lamins-deficient tumor cells could represent a good target for radiation therapy. ..
- Kubben N, Voncken J, Demmers J, Calis C, van Almen G, Pinto Y, et al. Identification of differential protein interactors of lamin A and progerin. Nucleus. 2010;1:513-25 pubmed publisher..We identified a total of 313 lamina-interacting proteins, including several novel lamin A interactors, and we characterize a set of 35 proteins which preferentially interact with lamin A or progerin. ..
- Khatau S, Kim D, Hale C, Bloom R, Wirtz D. The perinuclear actin cap in health and disease. Nucleus. 2010;1:337-42 pubmed publisher..The perinuclear actin cap may also be a mediator of microenvironment mechanosensing and mechanotransduction, as well as a regulator of cell motility, polarization and differentiation. ..
- Carboni N, Sardu C, Cocco E, Marrosu G, Manzi R, Nissardi V, et al. Cardiac involvement in patients with lamin A/C gene mutations: a cohort observation. Muscle Nerve. 2012;46:187-92 pubmed publisher..Cardiac involvement represents a very common phenotypic expression of LMNA gene mutation. Subjects sharing common genetic background seem to suffer from analogue pattern of cardiac manifestation. ..
- Rodriguez J, Calvo F, Gonzalez J, Casar B, Andres V, Crespo P. ERK1/2 MAP kinases promote cell cycle entry by rapid, kinase-independent disruption of retinoblastoma-lamin A complexes. J Cell Biol. 2010;191:967-79 pubmed publisher..We also show that cellular transformation and tumor cell proliferation are dependent on the balance between lamin A and nuclear ERK1/2 levels, which determines Rb accessibility for phosphorylation/inactivation. ..
- Małek L, Labib S, Mazurkiewicz L, Saj M, Płoski R, Tesson F, et al. A new c.1621 C > G, p.R541G lamin A/C mutation in a family with DCM and regional wall motion abnormalities (akinesis/dyskinesis): genotype-phenotype correlation. J Hum Genet. 2011;56:83-6 pubmed publisher..1621 C > G, p.R541G substitution whose pathogenicity was confirmed by transfection of mouse myoblasts. Our results emphasize the role of LMNA mutations at position R541 in DCM cases with segmental LV wall motion akinesis/dyskinesis. ..
- Gurudatta B, Shashidhara L, Parnaik V. Lamin C and chromatin organization in Drosophila. J Genet. 2010;89:37-49 pubmed..Our results suggest that Drosophila lamC has a tissue-specific role during development and is required for chromatin organization. ..
- Capo Chichi C, Cai K, Smedberg J, Ganjei Azar P, Godwin A, Xu X. Loss of A-type lamin expression compromises nuclear envelope integrity in breast cancer. Chin J Cancer. 2011;30:415-25 pubmed..We conclude that the loss of nuclear envelope structural proteins lamin A/C in breast cancer underlies the two hallmarks of cancer aberrations in nuclear morphology and aneuploidy. ..
- Liang L, Zhang H, Gu X. Homozygous LMNA mutation R527C in atypical Hutchinson-Gilford progeria syndrome: evidence for autosomal recessive inheritance. Acta Paediatr. 2009;98:1365-8 pubmed publisher..Heterozygous carrier status 1579C>T was detected in both of the asymptomatic parents. Homozygous mutation R527C in LMNA yields atypical HGPS, and it suggests an autosomal recessive inheritance in this family. ..
- Ostlund C, Folker E, Choi J, Gomes E, Gundersen G, Worman H. Dynamics and molecular interactions of linker of nucleoskeleton and cytoskeleton (LINC) complex proteins. J Cell Sci. 2009;122:4099-108 pubmed publisher..Our data support a model in which A-type lamins and Sun2 anchor nesprin-2 in the outer nuclear membrane, whereas emerin, Sun1 and actin are dispensable for this anchoring. ..
- Dreesen O, Stewart C. Accelerated aging syndromes, are they relevant to normal human aging?. Aging (Albany NY). 2011;3:889-95 pubmed..Whether persistent DNA damage, particularly at telomeres, is the root cause for these pathologies remains to be established, since not all progeroid Lmna mutations result in DNA damage and genome instability. ..
- Burtner C, Kennedy B. Progeria syndromes and ageing: what is the connection?. Nat Rev Mol Cell Biol. 2010;11:567-78 pubmed publisher..These observations, coupled with genetic studies of longevity, lead to a hypothesis whereby progeria syndromes accelerate a subset of the pathological changes that together drive the normal ageing process. ..
- Brauch K, Chen L, Olson T. Comprehensive mutation scanning of LMNA in 268 patients with lone atrial fibrillation. Am J Cardiol. 2009;103:1426-8 pubmed publisher..Comprehensive mutation scanning identified only 1 potentially pathogenic mutation. In conclusion, LMNA mutations rarely cause lone AF and routine genetic testing of LMNA in these patients does not appear warranted. ..
- Ho J, Zhou T, Lai W, Huang Y, Chan Y, Li X, et al. Generation of induced pluripotent stem cell lines from 3 distinct laminopathies bearing heterogeneous mutations in lamin A/C. Aging (Albany NY). 2011;3:380-90 pubmed
- Coffinier C, Jung H, Li Z, Nobumori C, Yun U, Farber E, et al. Direct synthesis of lamin A, bypassing prelamin a processing, causes misshapen nuclei in fibroblasts but no detectable pathology in mice. J Biol Chem. 2010;285:20818-26 pubmed publisher..We conclude that prelamin A processing is dispensable in mice and that direct synthesis of mature lamin A has little if any effect on the targeting of lamin A to the nuclear rim in mouse tissues. ..
- Jahn D, Schramm S, Schnolzer M, Heilmann C, de Koster C, Schütz W, et al. A truncated lamin A in the Lmna -/- mouse line: implications for the understanding of laminopathies. Nucleus. 2012;3:463-74 pubmed publisher..Based on our findings we discuss implications for the interpretation of previous studies using Lmna (-/-) mice and the concept of human laminopathies. ..
- Bertacchini J, Beretti F, Cenni V, Guida M, Gibellini F, Mediani L, et al. The protein kinase Akt/PKB regulates both prelamin A degradation and Lmna gene expression. FASEB J. 2013;27:2145-55 pubmed publisher..Moreover, given the large number of diseases related to prelamin A, our findings represent a further important step bridging basic A-type lamin physiology to therapeutic approaches for lamin A-linked disorders. ..
- Reunert J, Wentzell R, Walter M, Jakubiczka S, Zenker M, Brune T, et al. Neonatal progeria: increased ratio of progerin to lamin A leads to progeria of the newborn. Eur J Hum Genet. 2012;20:933-7 pubmed publisher..It is suggestive that the ratio of farnesylated protein to mature lamin A determines the disease severity in progeria. ..
- Puente X, Quesada V, Osorio F, Cabanillas R, Cadinanos J, Fraile J, et al. Exome sequencing and functional analysis identifies BANF1 mutation as the cause of a hereditary progeroid syndrome. Am J Hum Genet. 2011;88:650-6 pubmed publisher..These data demonstrate the utility of exome sequencing for identifying the cause of rare Mendelian disorders and underscore the importance of nuclear envelope alterations in human aging. ..
- Muchir A, Reilly S, Wu W, Iwata S, Homma S, Bonne G, et al. Treatment with selumetinib preserves cardiac function and improves survival in cardiomyopathy caused by mutation in the lamin A/C gene. Cardiovasc Res. 2012;93:311-9 pubmed publisher..Our results suggest that selumetinib or other related inhibitors that have been safely administered to humans in clinical trials could potentially be used to treat LMNA cardiomyopathy. ..
- Lopez Mejia I, Vautrot V, de Toledo M, Behm Ansmant I, Bourgeois C, Navarro C, et al. A conserved splicing mechanism of the LMNA gene controls premature aging. Hum Mol Genet. 2011;20:4540-55 pubmed publisher..Genetic and biochemical data together favor the view that physiological progerin production is under tight control of a conserved splicing mechanism to avoid precocious aging. ..
- Taimen P, Pfleghaar K, Shimi T, Möller D, Ben Harush K, Erdos M, et al. A progeria mutation reveals functions for lamin A in nuclear assembly, architecture, and chromosome organization. Proc Natl Acad Sci U S A. 2009;106:20788-93 pubmed publisher..The study also emphasizes the importance of lamins in nuclear assembly and chromatin organization. ..
- Madej Pilarczyk A, Rosińska Borkowska D, Rekawek J, Marchel M, Szaluś E, Jabłońska S, et al. Progeroid syndrome with scleroderma-like skin changes associated with homozygous R435C LMNA mutation. Am J Med Genet A. 2009;149A:2387-92 pubmed publisher..Scleroderma-like skin changes in infants, associated with growth retardation and dysmorphic features, suggest premature aging syndrome, requiring genetic testing and counseling of asymptomatic carriers of LMNA mutations. ..
- Saga A, Karibe A, Otomo J, Iwabuchi K, Takahashi T, Kanno H, et al. Lamin A/C gene mutations in familial cardiomyopathy with advanced atrioventricular block and arrhythmia. Tohoku J Exp Med. 2009;218:309-16 pubmed..Screening of LMNA mutation might be beneficial for risk stratification and clinical management of this type of unclassified familial cardiomyopathy. ..
- Jung H, Coffinier C, Choe Y, Beigneux A, Davies B, Yang S, et al. Regulation of prelamin A but not lamin C by miR-9, a brain-specific microRNA. Proc Natl Acad Sci U S A. 2012;109:E423-31 pubmed publisher..The down-regulation of prelamin A expression in the brain could explain why mouse models of Hutchinson-Gilford progeria syndrome are free of central nervous system pathology. ..
- Bidault G, Vatier C, Capeau J, Vigouroux C, Bereziat V. LMNA-linked lipodystrophies: from altered fat distribution to cellular alterations. Biochem Soc Trans. 2011;39:1752-7 pubmed publisher..In the present review, we describe the clinical phenotype of LMNA-linked lipodystrophies and discuss the current physiological and biochemical hypotheses regarding the pathophysiology of these diseases. ..
- Bertrand A, Renou L, Papadopoulos A, Beuvin M, Lacene E, Massart C, et al. DelK32-lamin A/C has abnormal location and induces incomplete tissue maturation and severe metabolic defects leading to premature death. Hum Mol Genet. 2012;21:1037-48 pubmed publisher..And importantly, L-CMD patients should be investigated for putative metabolic disorders. ..
- Pekovic V, Gibbs Seymour I, Markiewicz E, Alzoghaibi F, Benham A, Edwards R, et al. Conserved cysteine residues in the mammalian lamin A tail are essential for cellular responses to ROS generation. Aging Cell. 2011;10:1067-79 pubmed publisher..Our findings suggest that the conserved C-terminal cysteine residues are essential for lamin A function and that loss or oxidative damage to these cysteine residues promotes cellular senescence. ..
- Le Dour C, Schneebeli S, Bakiri F, Darcel F, Jacquemont M, Maubert M, et al. A homozygous mutation of prelamin-A preventing its farnesylation and maturation leads to a severe lipodystrophic phenotype: new insights into the pathogenicity of nonfarnesylated prelamin-A. J Clin Endocrinol Metab. 2011;96:E856-62 pubmed publisher
- Nikolova Krstevski V, Leimena C, Xiao X, Kesteven S, Tan J, Yeo L, et al. Nesprin-1 and actin contribute to nuclear and cytoskeletal defects in lamin A/C-deficient cardiomyopathy. J Mol Cell Cardiol. 2011;50:479-86 pubmed publisher..Changes in the distribution and expression patterns of nuclear and cytoskeletal actin suggest that diverse transcriptional and structural defects may also contribute to DCM in Lmna(-/-) mice. ..
- De Vos W, Houben F, Hoebe R, Hennekam R, van Engelen B, Manders E, et al. Increased plasticity of the nuclear envelope and hypermobility of telomeres due to the loss of A-type lamins. Biochim Biophys Acta. 2010;1800:448-58 pubmed publisher..Because of the pivotal role of dynamics in nuclear function, these differences likely contribute to or represent novel mechanisms in laminopathy development. ..
- Uhlírová R, Horáková A, Galiova G, Legartova S, Matula P, Fojtova M, et al. SUV39h- and A-type lamin-dependent telomere nuclear rearrangement. J Cell Biochem. 2010;109:915-26 pubmed publisher..Taken together, our data show that SUV39h and A-type lamins likely play a key role in telomere maintenance and telomere nuclear architecture. ..
- Haque F, Mazzeo D, Patel J, Smallwood D, Ellis J, Shanahan C, et al. Mammalian SUN protein interaction networks at the inner nuclear membrane and their role in laminopathy disease processes. J Biol Chem. 2010;285:3487-98 pubmed publisher..We propose that these different perturbations in lamin A-SUN protein interactions may underlie the opposing effects of EDMD and HGPS mutations on nuclear and cellular mechanics. ..
- Kane M, Lindsay M, Judge D, Barrowman J, Ap Rhys C, Simonson L, et al. LMNA-associated cardiocutaneous progeria: an inherited autosomal dominant premature aging syndrome with late onset. Am J Med Genet A. 2013;161A:1599-611 pubmed publisher..Our findings advance knowledge of human LMNA progeria syndromes, and raise the possibility that typical and atypical progerias may converge upon a common mechanism to cause premature aging disease. ..