ArticleHuman molecular genetics2010
An accumulation of non-farnesylated prelamin A causes cardiomyopathy but not progeria.
Article in Human molecular genetics, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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Who cites it
64 citing papers in PubMed, 104 citations in OpenAlex.
- The accumulation of progerin underlies the loss of aortic smooth muscle cells in Hutchinson-Gilford progeria syndrome.Cell death & disease · 2025Article
- Roles of the lamin A-specific tail region in the localization to sites of nuclear envelope rupture.PNAS nexus · 2024Article
- Lipodystrophic Laminopathies: From Dunnigan Disease to Progeroid Syndromes.International journal of molecular sciences · 2024Review
- Genetic and pharmacological modulation of lamin A farnesylation determines its function and turnover.Aging cell · 2024Article
- Defective prelamin A processing promotes unconventional necroptosis driven by nuclear RIPK1.Nature cell biology · 2024Article
- Effect of β-Estradiol on Adipogenesis in a 3T3-L1 Cell Model of Prelamin A Accumulation.International journal of molecular sciences · 2024Article
- Revisiting the truncated lamin A produced by a commonly used strain ofNucleus (Austin, Tex.) · 2023Article
- Impaired end joining induces cardiac atrophy in a Hutchinson-Gilford progeria mouse model.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Naturally occurring canine laminopathy leading to a dilated and fibrosing cardiomyopathy in the Nova Scotia Duck Tolling Retriever.Scientific reports · 2023Article
- The lipoprotein lipase that is shuttled into capillaries by GPIHBP1 enters the glycocalyx where it mediates lipoprotein processing.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Systematic in vivo candidate evaluation uncovers therapeutic targets for LMNA dilated cardiomyopathy and risk of Lamin A toxicity.Journal of translational medicine · 2023Article
- The Molecular and Cellular Basis of Hutchinson-Gilford Progeria Syndrome and Potential Treatments.Genes · 2023Review
- Lamin A precursor localizes to the Z-disc of sarcomeres in the heart and is dynamically regulated in muscle cell differentiation.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2022Article
- Lamin A to Z in normal aging.Aging · 2022Article
- Status of treatment strategies for Hutchinson-Gilford progeria syndrome with a focus on prelamin: A posttranslational modification.Basic & clinical pharmacology & toxicology · 2022Review
- In vivo cyclic induction of the FOXM1 transcription factor delays natural and progeroid aging phenotypes and extends healthspan.Nature aging · 2022Article
- Abolishing the prelamin A ZMPSTE24 cleavage site leads to progeroid phenotypes with near-normal longevity in mice.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Preclinical Advances of Therapies for Laminopathies.Journal of clinical medicine · 2021Review
- Progress and trends in the development of therapies for Hutchinson-Gilford progeria syndrome.Aging cell · 2020Review
- Deficiency in ZMPSTE24 and resulting farnesyl-prelamin A accumulation only modestly affect mouse adipose tissue stores.Journal of lipid research · 2020Article
4 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Lamin A is formed from prelamin A by four post-translational processing steps-farnesylation, release of the last three amino acids of the protein, methylation of the farnesylcysteine and the endoproteolytic release of the C-terminal 15 amino acids (including the farnesylcysteine methyl ester). When the final processing step does not occur, a farnesylated and methylated prelamin A accumulates in cells, causing a severe progeroid disease, restrictive dermopathy (RD). Whether RD is caused by the retention of farnesyl lipid on prelamin A, or by the retention of the last 15 amino acids of the protein, is unknown. To address this issue, we created knock-in mice harboring a mutant Lmna allele (LmnanPLAO) that yields exclusively non-farnesylated prelamin A (and no lamin C). These mice had no evidence of progeria but succumbed to cardiomyopathy. We suspected that the non-farnesylated prelamin A in the tissues of these mice would be strikingly mislocalized to the nucleoplasm, but this was not the case; most was at the nuclear rim (indistinguishable from the lamin A in wild-type mice). The cardiomyopathy could not be ascribed to an absence of lamin C because mice expressing an otherwise identical knock-in allele yielding only wild-type prelamin A appeared normal. We conclude that lamin C synthesis is dispensable in mice and that the failure to convert prelamin A to mature lamin A causes cardiomyopathy (at least in the absence of lamin C). The latter finding is potentially relevant to the long-term use of protein farnesyltransferase inhibitors, which lead to an accumulation of non-farnesylated prelamin A.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.