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Just at the beginning of the millennium the neologism laminopathies has been introduced in the scientific vocabulary. An exponential increase of interest on the subject started concomitantly, so that a formerly quite neglected group of... more
Just at the beginning of the millennium the neologism laminopathies has been introduced in the scientific vocabulary. An exponential increase of interest on the subject started concomitantly, so that a formerly quite neglected group of rare human diseases is now widely investigated. This review will cover the history of the identification of the molecular basis for fourteen (since now) hereditary diseases arising from defects in genes that encode nuclear envelope and nuclear lamina-associated proteins and will also consider the hypotheses that can account for the role of structural nuclear proteins in the pathogenesis of diseases affecting a wide spectrum of tissues.
Publication Date: 2005
Publication Name: Journal of Cellular Physiology
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Lamin A is a key component of the nuclear lamina produced through post-translational processing of its precursor known as prelamin A.LMNA mutations leading to farnesylated prelamin A accumulation are known to cause lipodystrophy,... more
Lamin A is a key component of the nuclear lamina produced through post-translational processing of its precursor known as prelamin A.LMNA mutations leading to farnesylated prelamin A accumulation are known to cause lipodystrophy, progeroid and developmental diseases, including Mandibuloacral dysplasia, a mild progeroid syndrome with partial lipodystrophy and altered bone turnover. Thus, degradation of prelamin A is expected to improve the disease phenotype. Here, we show different susceptibilities of prelamin A forms to proteolysis and further demonstrate that treatment with rapamycin efficiently and selectively triggers lysosomal degradation of farnesylated prelamin A, the most toxic processing intermediate. Importantly, rapamycin treatment of Mandibuloacral dysplasia cells, which feature very low levels of the NAD-dependent sirtuin SIRT-1 in the nuclear matrix, restores SIRT-1 localization and distribution of chromatin markers, elicits release of the transcription factor Oct-1 and...
Publication Date: 2014
Publication Name: Aging
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Publication Date: 2007
Publication Name: Journal of Cellular Biochemistry
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Publication Date: 2005
Publication Name: Human Molecular Genetics
Research Interests: Western blotting, Biological Sciences, Adipose tissue, Cell Differentiation, Humans, and 15 moreMice, Animals, Human Molecular Genetics, Peroxisome proliferator-activated receptor, Lipid metabolism, Transcription Factor, Immunoprecipitation, Nuclear envelope, Cell nucleus, Fluorescent Antibody Technique, Adipocytes, Body Fat, Human Fibroblasts, Protein Binding, and Lipodystrophy
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Publication Date: 2012
Publication Name: Histochemistry and Cell Biology
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Publication Date: 2003
Publication Name: Experimental Cell Research
Research Interests: Electron Microscopy, RNA, Membrane Proteins, Humans, Insulin, and 13 moreMutation, Alternative splicing, Clinical Sciences, Lamins, Nuclear envelope, Body Fat, Alternative Splicing, Human Fibroblasts, Intermolecular Interaction, Biochemistry and cell biology, Heterochromatin, Interphase, and Lipodystrophy
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Publication Date: 2013
Publication Name: European Journal of Histochemistry
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by Stefano Squarzoni and C. Capanni
Publication Date: 2005
Publication Name: Cellular and Molecular Life Sciences
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Publication Date: 2011
Publication Name: Cell Death and Differentiation
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Publication Date: 2012
Publication Name: Cell Cycle
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Lamin A, a protein component of the nuclear lamina, is synthesized as a precursor named prelamin A, whose multi-step maturation process involves different protein intermediates. As demonstrated in laminopathies such as familial partial... more
Lamin A, a protein component of the nuclear lamina, is synthesized as a precursor named prelamin A, whose multi-step maturation process involves different protein intermediates. As demonstrated in laminopathies such as familial partial lipodystrophy, mandibuloacral dysplasia, Werner syndrome, Hutchinson-Gilford progeria syndrome and restrictive dermopathy, failure of prelamin A processing results in the accumulation of lamin A protein precursors inside the nucleus which dominantly produces aberrant chromatin structure. To understand if nuclear lamina components may be involved in prelamin A chromatin remodeling effects, we investigated barrier-to-autointegration factor (BAF) localization and expression in prelamin A accumulating cells. BAF is a DNA-binding protein that interacts directly with histones, lamins and LEM-domain proteins and has roles in chromatin structure, mitosis and gene regulation. In this study, we show that the BAF heterogeneous localization between nucleus and cytoplasm observed in HEK293 cycling cells changes in response to prelamin A accumulation. In particular, we observed that the accumulation of lamin A, non-farnesylated prelamin A and farnesylated carboxymethylated lamin A precursors induce BAF nuclear translocation. Moreover, we show that the treatment of human fibroblasts with prelamin A interfering drugs results in similar changes. Finally, we report that the accumulation of progerin, a truncated form of farnesylated and carboxymethylated prelamin A identified in Hutchinson-Gilford progeria syndrome cells, induces BAF recruitment in the nucleus. These findings are supported by coimmunoprecipitation of prelamin A or progerin with BAF in vivo and suggest that BAF could mediate prelamin A-induced chromatin effects.
Publication Date: 2010
Publication Name: Cell Cycle
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Publication Date: 2009
Publication Name: Biology of the Cell
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Changes in vimentin, lamin A/C and mitofilin induce aberrant cell organization in fibroblasts from Fanconi anemia complementation group A (FA-A) patientsmore
by C. Capanni
Growing number of publication has proved an increasing of cellular function of the Fanconi anemia proteins. To chromosome stability and DNA repair new roles have been attributed to FA proteins in oxidative stress response and homeostasis,... more
Growing number of publication has proved an increasing of cellular function of the Fanconi anemia proteins. To chromosome stability and DNA repair new roles have been attributed to FA proteins in oxidative stress response and homeostasis, immune response and cytokines sensibility, gene expression. Our work shows a new role for FA-A protein: the organization of the cellular structure. By 2D-PAGE of FA-A and correct fibroblasts treated and untreated with H2O2 we identify different expression of protein involved in the structural organization of nucleus, intermediate filaments and mitochondria. Immunofluorescence and electronic microscopy analysis clearly show an already altered cellular structure in normal culture condition and this worsted after oxidative stress. FA-A cell appears structurally prone to physiologic stress and this could explain part of the phenotype of FA cells.
Publication Date: 2013
Publication Name: Biochimie
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by Stefano Squarzoni and C. Capanni
Nitric oxide synthases (NOS) are different widely expressed enzymes which produce the molecular messenger nitric oxide. The neuronal isoform of NOS (nNOS) is involved in several processes of the cell metabolism, most of which are, at... more
Nitric oxide synthases (NOS) are different widely expressed enzymes which produce the molecular messenger nitric oxide. The neuronal isoform of NOS (nNOS) is involved in several processes of the cell metabolism, most of which are, at present, not fully understood (neurotransmission, smooth muscle motility, myoblast and myocyte biology and others). In skeletal muscle nNOS is present mainly at the plasmalemma, where it is attached to the dystrophin-related proteins; in fact, in pathologies involving dystrophin, nNOS is altered as well. We report that in aged rats the nNOS amount in skeletal muscle increases both in the soluble and microsomal fractions and that an additional intracytoplasmic localisation appears.
Publication Date: 1998
Publication Name: Biochemical and Biophysical Research Communications
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Publication Date: 2000
Publication Name: Acta Neuropathologica
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