ArticleThe Journal of biological chemistry2010
Direct synthesis of lamin A, bypassing prelamin a processing, causes misshapen nuclei in fibroblasts but no detectable pathology in mice.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 80 citations in OpenAlex.
- The Underexplored Mechanobiology of Lamin A Biogenesis and Homeostasis.Biology of the cell · 2026Review
- Nuclear dysfunction in aging and neurodegeneration.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- Perinuclear organelle trauma at the nexus of cardiomyopathy pathogenesis arising from loss of functionNucleus (Austin, Tex.) · 2025Review
- Roles of the lamin A-specific tail region in the localization to sites of nuclear envelope rupture.PNAS nexus · 2024Article
- N-terminal tags impair the ability of lamin A to provide structural support to the nucleus.Journal of cell science · 2024Article
- Actin contraction controls nuclear blebbing and rupture independent of actin confinement.Molecular biology of the cell · 2024Article
- Systematic in vivo candidate evaluation uncovers therapeutic targets for LMNA dilated cardiomyopathy and risk of Lamin A toxicity.Journal of translational medicine · 2023Article
- Progerin, an Aberrant Spliced Form of Lamin A, Is a Potential Therapeutic Target for HGPS.Cells · 2023Review
- Epigenetics inCells · 2023Review
- Progerin-Induced Impairment in Wound Healing and Proliferation in Vascular Endothelial Cells.Frontiers in aging · 2022Article
- Lamin C is required to establish genome organization after mitosis.Genome biology · 2021Article
- Nuclear membrane ruptures, cell death, and tissue damage in the setting of nuclear lamin deficiencies.Nucleus (Austin, Tex.) · 2020Review
- Pharmacotherapy to gene editing: potential therapeutic approaches for Hutchinson-Gilford progeria syndrome.GeroScience · 2020Review
- Deficiency in ZMPSTE24 and resulting farnesyl-prelamin A accumulation only modestly affect mouse adipose tissue stores.Journal of lipid research · 2020Article
- Review
- Nuclear mechanosensing.Emerging topics in life sciences · 2018Article
- Nuclear rupture at sites of high curvature compromises retention of DNA repair factors.The Journal of cell biology · 2018Article
- Review
- OGT (Cells · 2018Article
- Lamins and Lamin-Associated Proteins in Gastrointestinal Health and Disease.Gastroenterology · 2018Review
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
Abstract
Lamin A, a key component of the nuclear lamina, is generated from prelamin A by four post-translational processing steps: farnesylation, endoproteolytic release of the last three amino acids of the protein, methylation of the C-terminal farnesylcysteine, and finally, endoproteolytic release of the last 15 amino acids of the protein (including the farnesylcysteine methyl ester). The last cleavage step, mediated by ZMPSTE24, releases mature lamin A. This processing scheme has been conserved through vertebrate evolution and is widely assumed to be crucial for targeting lamin A to the nuclear envelope. However, its physiologic importance has never been tested. To address this issue, we created mice with a "mature lamin A-only" allele (Lmna(LAO)), which contains a stop codon immediately after the last codon of mature lamin A. Thus, Lmna(LAO/LAO) mice synthesize mature lamin A directly, bypassing prelamin A synthesis and processing. The levels of mature lamin A in Lmna(LAO/LAO) mice were indistinguishable from those in "prelamin A-only" mice (Lmna(PLAO/PLAO)), where all of the lamin A is produced from prelamin A. Lmna(LAO/LAO) exhibited normal body weights and had no detectable disease phenotypes. A higher frequency of nuclear blebs was observed in Lmna(LAO/LAO) embryonic fibroblasts; however, the mature lamin A in the tissues of Lmna(LAO/LAO) mice was positioned normally at the nuclear rim. We conclude that prelamin A processing is dispensable in mice and that direct synthesis of mature lamin A has little if any effect on the targeting of lamin A to the nuclear rim in mouse tissues.
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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.