Background: Lamins, key nuclear lamina components, have been proposed as candidate risk biomarkers in different types of cancer but their accuracy is still debated. AKTIP is a telomeric protein with the property of being enriched at the nuclear lamina. AKTIP has similarity with the tumor susceptibility gene TSG101.
View Article and Find Full Text PDFTo complete mitosis, the bridge that links the two daughter cells needs to be cleaved. This step is carried out by the endosomal sorting complex required for transport (ESCRT) machinery. AKTIP, a protein discovered to be associated with telomeres and the nuclear membrane in interphase cells, shares sequence similarities with the ESCRT I component TSG101.
View Article and Find Full Text PDFMutations in the LaminA gene are a common cause of monogenic dilated cardiomyopathy. Here we show that mice with a cardiomyocyte-specific Lmna deletion develop cardiac failure and die within 3-4 weeks after inducing the mutation. When the same Lmna mutations are induced in mice genetically deficient in the LINC complex protein SUN1, life is extended to more than one year.
View Article and Find Full Text PDFHutchinson-Gilford progeria is a premature aging syndrome caused by a truncated form of lamin A called progerin. Progerin expression results in a variety of cellular defects including heterochromatin loss, DNA damage, impaired proliferation and premature senescence. It remains unclear how these different progerin-induced phenotypes are temporally and mechanistically linked.
View Article and Find Full Text PDFProtein-protein interactions (PPIs) add an essential layer of complexity to the information encoded by the genome. Modulation of such interactions is a key feature of most, if not all, cellular activities and allows cells to respond rapidly to both internal and external signals and stimuli. In this respect, the development of the BioID assay to interrogate PPIs within a cellular context represents an important adjunct to the range of tools currently at researchers' disposal.
View Article and Find Full Text PDFThe modulation of protein-protein interactions (PPIs) is an essential regulatory activity defining diverse cell functions in development and disease. BioID is an unbiased proximity-dependent biotinylation method making use of a biotin-protein ligase fused to a protein of interest and has become an important tool for mapping of PPIs within cellular contexts. We devised an advanced method, 2C-BioID, in which the biotin-protein ligase is kept separate from the protein of interest, until the two are induced to associate by the addition of a dimerizing agent.
View Article and Find Full Text PDFSkin ageing is an inevitable consequence of life and accelerated by exposure to ultraviolet (UV) rays. Senescence is an irreversible growth arrest and senescent cells accumulate in ageing tissues, at sites of age-related pathologies and in pre-neoplastic lesions. Conventionally, senescent cells have been detected by senescence associated-β-galactosidase (SA-β-gal) staining, a procedure that requires enzymatic activity, which is lost in fixed tissue samples.
View Article and Find Full Text PDFThe nuclear lamina is a universal feature of metazoan nuclear envelopes (NEs) [1]. In mammalian cells, it appears as a 10-30 nm filamentous layer at the nuclear face of the inner nuclear membrane (INM) and is composed primarily of A- and B-type lamins, members of the intermediate filament family [2]. While providing structural integrity to the NE, the lamina also represents an important signaling and regulatory platform [3].
View Article and Find Full Text PDFHutchinson-Gilford progeria (HGPS) is a premature ageing syndrome caused by a mutation in LMNA, resulting in a truncated form of lamin A called progerin. Progerin triggers loss of the heterochromatic marker H3K27me3, and premature senescence, which is prevented by telomerase. However, the mechanism how progerin causes disease remains unclear.
View Article and Find Full Text PDFThe intermediate filament A- and B-type lamins are key architectural components of the nuclear lamina, a proteinaceous meshwork that lies underneath the inner nuclear membrane. In the past decade, many different monogenic human diseases have been linked to mutations in various components of the nuclear lamina. Mutations in LMNA (encoding lamin A and C) cause a variety of human diseases, collectively called laminopathies.
View Article and Find Full Text PDFThe nuclear lamina underlies the inner nuclear membrane and consists of a proteinaceous meshwork of intermediate filaments: the A- and B-type lamins. Mutations in LMNA (encoding lamin A and C) give rise to a variety of human diseases including muscular dystrophies, cardiomyopathies and the premature aging syndrome progeria (HGPS). Duplication of the LMNB1 locus, leading to elevated levels of lamin B1, causes adult-onset autosomal dominant leukodystrophy (ADLD), a rare genetic disease that leads to demyelination in the central nervous system (CNS).
View Article and Find Full Text PDFThe nuclear lamina consists of A- and B-type lamins. Mutations in LMNA cause many human diseases, including progeria, a premature aging syndrome, whereas LMNB1 duplication causes adult-onset autosomal dominant leukodystrophy (ADLD). LMNB1 is reduced in cells from progeria patients, but the significance of this reduction is unclear.
View Article and Find Full Text PDFLoss of function of the myotubularin (MTM)-related protein 2 (MTMR2) in Schwann cells causes Charcot-Marie-Tooth disease type 4B1, a severe demyelinating neuropathy, but the consequences of MTMR2 disruption in Schwann cells are unknown. We established the expression profile of MTMR2 by real-time RT-PCR during rat myelination and showed it to be preferentially expressed at the onset of the myelination period. We developed a model in which MTMR2 loss of function was reproduced in primary cultures of Schwann cells by RNA interference.
View Article and Find Full Text PDFExperimental transplantation in rodent models of CNS demyelination has led to the idea that Schwann cells may be candidates for cell therapy in human myelin diseases. Here we investigated the ability of Schwann cells autografts to generate myelin in the demyelinated monkey spinal cord. We report that monkey Schwann cells derived from adult peripheral nerve biopsies retain, after growth factor expansion and transduction with a lentiviral vector encoding green fluorescent protein, the ability to differentiate in vitro into promyelinating cells.
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