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  • LMNA
  • Mutations associated with FPL have been reported in LMNA (lamin A/C), PPARG (PPARγ), AKT2 (AKT serine/threonine kinase 2), PLIN1 (perilipin-1), and CIDEC (cell-death-inducing DFFA-like effector B). Six types (1-6) have been described. (wikipedia.org)
  • Type 2 (Dunnigan Variety, FPL2) is the most common form and is due to mutations in the LMNA gene. (wikipedia.org)
  • This review summarizes the clinical characteristics of this disease, the underlying mutation in the lamin A (LMNA) gene that results in this phenotype and the recent advances in treatment strategies. (spotidoc.com)
  • FPLD results from mutations in LMNA gene, which is the gene that encodes nuclear lamins A and C. Familial partial lipodystrophy Hegele, RA (December 2000). (wikipedia.org)
  • hypertension
  • FPLD recapitulates the main metabolic attributes of the insulin resistance syndrome, including central obesity, hyperinsulinemia, glucose intolerance and diabetes usually type 2, dyslipidemia, hypertension, and early endpoints of atherosclerosis. (wikipedia.org)
  • mature lamin
  • Consequently, no mature lamin A is formed, and a farnesylated mutant prelamin A (progerin) accumulates in cells. (wikipedia.org)
  • This version of the protein is also referred to as prelamin A. Farnesylated prelamin A is further processed into mature lamin A by a metalloproteinase removing the last 15 amino acids and its farnesylated cysteine. (wikipedia.org)
  • This post-translationally modified cysteine residue is removed from prelamin A when it is endoproteolytically processed into mature lamin A. The protein encoded by this gene binds to the prenylated prelamin A carboxyl-terminal tail domain. (wikipedia.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)
  • 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)
  • chromatin
  • 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)
  • It has been shown that lamin polypeptides have an affinity for binding chromatin through their α-helical (rod like) domains at specific DNA sequences called matrix attachment regions (MAR). A MAR has a length of approximately 300-1000 bp and has a high A/T content. (wikipedia.org)
  • During this time period, investigations of rat liver nuclei revealed that lamins have an architectural relationship with chromatin and nuclear pores. (wikipedia.org)
  • defects
  • Defects in nuclear structure and function promote dilated cardiomyopathy in lamin A/C-deficient mice. (semanticscholar.org)
  • Defects in the expression of B-type lamins appear to have more severe effects, and very few defects have been described in the expression of B-type lamins with established pathologies. (biologists.org)
  • By contrast, larval muscle-specific expression of a truncated form of Lamin C lacking the N-terminal head (Lamin C DeltaN) caused muscle defects and semi-lethality, with adult 'escapers' possessing malformed legs. (umassmed.edu)
  • nuclei
  • 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. (biologists.org)
  • Eukaryotes usually have a single nucleus, but a few cell types, such as mammalian red blood cells, have no nuclei, and a few others have many. (wikipedia.org)
  • vitro
  • 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)
  • phosphorylation
  • A ) The phosphorylation site, residue Ser458, is highly conserved in evolution, as shown by amino acid sequence alignment of a portion of the Ig-fold domain of A-type lamins (amino acids 450−469) in vertebrates and invertebrates. (biologists.org)
  • After phosphorylation by cyclin B/Cdk1, the nuclear lamina depolymerises and B-type lamins stay associated with the fragments of the nuclear envelope whereas A-type lamins remain completely soluble throughout the remainder of the mitotic phase. (wikipedia.org)
  • structural
  • When lamin B1 expression was depleted, inhibition of RNA synthesis correlated with complex structural changes within the nucleolar active centers until, eventually, the nucleoli were dispersed completely. (biologists.org)
  • With normal lamin expression, the nucleoli were highly plastic, with dramatic and freely reversible structural changes correlating with the demand for ribosome biogenesis. (biologists.org)
  • We have surprisingly little knowledge of the molecular mechanisms that link nuclear function to structural nuclear elements such as the lamin-containing nucleoskeleton. (biologists.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)
  • Without lamin A, the nuclear lamina is unable to provide the nuclear envelope with adequate structural support, causing it to take on an abnormal shape. (wikipedia.org)
  • Expression
  • differences in baseline expression were not statistically significant between any cell type). (nih.gov)
  • 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)
  • The nuclear scaffold is predicted to be relatively permanent for a given cell type, but induction of a signaling pathway-by ligand binding, cell:cell contact, or some other mechanism-can temporarily shift the expression profile. (wikipedia.org)
  • LAP2alpha
  • Furthermore, selective disruption of A-type lamin structures by overexpression of lamin mutants in HeLa cells caused a redistribution of LAP2alpha. (biologists.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)
  • organisms
  • The presence of lamin polypeptides is an exclusive property of Metazoan organisms. (wikipedia.org)
  • Lamins are present in all members of the kingdom Animalia (Metazoa), but are not found in unicellular organisms, plants, or fungi. (wikipedia.org)
  • Lamins of higher level organisms, such as vertebrates, continue to assemble into paracrystalline arrays. (wikipedia.org)
  • Model organisms have been used in the study of Lamin B2 function. (wikipedia.org)
  • mutant
  • C2 myoblasts were transfected with Akt−HA constructs (wtAkt−HA or myrAkt−HA) and FLAG−lamin A constructs (WT: wild type, RW: Arg453Trp mutant, RW/SA: Arg453Trp/Ser458Ala mutant) for 48 hours. (biologists.org)
  • situ
  • 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)
  • homology
  • Analysis of a second keratin sequence revealed that the two types of keratins share only about 30% amino acid sequence homology but share similar patterns of secondary structure domains. (wikipedia.org)