ArticleHistochemistry and cell biology2012
Altered chromatin organization and SUN2 localization in mandibuloacral dysplasia are rescued by drug treatment.
Article in Histochemistry and cell biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 29 citations in OpenAlex.
- Lipodystrophic Laminopathies: From Dunnigan Disease to Progeroid Syndromes.International journal of molecular sciences · 2024Review
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- Lipodystrophy-associated progeroid syndromes.Hormones (Athens, Greece) · 2022Review
- KISS1R and ANKRD31 Cooperate to Enhance Leydig Cell Gene ExpressionFrontiers in cell and developmental biology · 2022Article
- Article
- The Diverse Cellular Functions of Inner Nuclear Membrane Proteins.Cold Spring Harbor perspectives in biology · 2021Review
- Cutaneous and metabolic defects associated with nuclear abnormalities in a transgenic mouse model expressing R527H lamin A mutation causing mandibuloacral dysplasia type A (MADA) syndrome.Acta myologica : myopathies and cardiomyopathies : official journal of the Mediterranean Society of Myology · 2020Article
- Multisystem Progeroid Syndrome With Lipodystrophy, Cardiomyopathy, and Nephropathy Due to anJournal of the Endocrine Society · 2020Article
- Loss of MTX2 causes mandibuloacral dysplasia and links mitochondrial dysfunction to altered nuclear morphology.Nature communications · 2020Article
- The Cutting Edge: The Role of mTOR Signaling in Laminopathies.International journal of molecular sciences · 2019Review
- Hutchinson-Gilford Progeria Syndrome-Current Status and Prospects for Gene Therapy Treatment.Cells · 2019Review
- Statins and Histone Deacetylase Inhibitors Affect Lamin A/C - Histone Deacetylase 2 Interaction in Human Cells.Frontiers in cell and developmental biology · 2019Article
- Review
- Potential therapeutic effects of the MTOR inhibitors for preventing ageing and progeria-related disorders.British journal of clinical pharmacology · 2016Review
- The telomeric protein AKTIP interacts with A- and B-type lamins and is involved in regulation of cellular senescence.Open biology · 2016Article
- SUN2 Overexpression Deforms Nuclear Shape and Inhibits HIV.Journal of virology · 2016Article
- Modulation of TGFbeta 2 levels by lamin A in U2-OS osteoblast-like cells: understanding the osteolytic process triggered by altered lamins.Oncotarget · 2015Article
- Article
- The Histochemistry and Cell Biology compendium: a review of 2012.Histochemistry and cell biology · 2013Review
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mandibuloacral dysplasia type A (MADA) is a rare laminopathy characterized by growth retardation, craniofacial anomalies, bone resorption at specific sites including clavicles, phalanges and mandibula, mottled cutaneous pigmentation, skin rigidity, partial lipodystrophy, and insulin resistance. The disorder is caused by recessive mutations of the LMNA gene encoding for A-type lamins. The molecular feature of MADA consists in the accumulation of the unprocessed lamin A precursor, which is detected at the nuclear rim and in intranuclear aggregates. Here, we report the characterization of prelamin A post-translational modifications in MADA cells that induce alterations in the chromatin arrangement and dislocation of nuclear envelope-associated proteins involved in correct nucleo-cytoskeleton relationships. We show that protein post-translational modifications change depending on the passage number, suggesting the onset of a feedback mechanism. Moreover, we show that treatment of MADA cells with the farnesyltransferase inhibitors is effective in the recovery of the chromatin phenotype, altered in MADA, provided that the cells are at low passage number, while at high passage number, the treatment results ineffective. Moreover, the distribution of the lamin A interaction partner SUN2, a constituent of the nuclear envelope, is altered by MADA mutations, as argued by the formation of a highly disorganized lattice. Treatment with statins partially rescues proper SUN2 organization, indicating that its alteration is caused by farnesylated prelamin A accumulation. Given the major role of SUN1 and SUN2 in the nucleo-cytoskeleton interactions and in regulation of nuclear positioning in differentiating cells, we hypothesise that mechanisms regulating nuclear membrane-centrosome interplay and nuclear movement may be affected in MADA fibroblasts.
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