| Hutchinson-Gilford progeria mutant lamin A primarily targets human vascular cells as detected by an anti-Lamin A G608G antibody. | |
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MedLine Citation:
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PMID: 16461887 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Hutchinson-Gilford progeria syndrome (HGPS; Online Mendelian Inheritance in Man accession no. 176670) is a rare disorder that is characterized by segmental premature aging and death between 7 and 20 years of age from severe premature atherosclerosis. Mutations in the LMNA gene are responsible for this syndrome. Approximately 80% of HGPS cases are caused by a G608 (GGC-->GGT) mutation within exon 11 of LMNA, which elicits a deletion of 50 aa near the C terminus of prelamin A. In this article, we present evidence that the mutant lamin A (progerin) accumulates in the nucleus in a cellular age-dependent manner. In human HGPS fibroblast cultures, we observed, concomitantly to nuclear progerin accumulation, severe nuclear envelope deformations and invaginations preventable by farnesyltransferase inhibition. Nuclear alterations affect cell-cycle progression and cell migration and elicit premature senescence. Strikingly, skin biopsy sections from a subject with HGPS showed that the truncated lamin A accumulates primarily in the nuclei of vascular cells. This finding suggests that accumulation of progerin is directly involved in vascular disease in progeria. |
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Authors:
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Dayle McClintock; Leslie B Gordon; Karima Djabali |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2006-02-06 |
Journal Detail:
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Title: Proceedings of the National Academy of Sciences of the United States of America Volume: 103 ISSN: 0027-8424 ISO Abbreviation: Proc. Natl. Acad. Sci. U.S.A. Publication Date: 2006 Feb |
Date Detail:
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Created Date: 2006-02-15 Completed Date: 2006-04-07 Revised Date: 2009-11-18 |
Medline Journal Info:
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Nlm Unique ID: 7505876 Medline TA: Proc Natl Acad Sci U S A Country: United States |
Other Details:
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Languages: eng Pagination: 2154-9 Citation Subset: IM |
Affiliation:
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Department of Dermatology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Age Factors Aging, Premature / genetics Antibodies Atherosclerosis / genetics Cell Movement Cell Nucleus / chemistry*, metabolism Cell Proliferation Cells, Cultured Endothelial Cells / chemistry, metabolism Enzyme Inhibitors / pharmacology Farnesyltranstransferase / antagonists & inhibitors Fibroblasts / chemistry, metabolism Humans Lamin Type A / analysis*, genetics*, metabolism Mutation Progeria / genetics, metabolism*, pathology Skin / pathology |
| Grant Support | |
ID/Acronym/Agency:
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K01AR048594/AR/NIAMS NIH HHS; R01AG025302/AG/NIA NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antibodies; 0/Enzyme Inhibitors; 0/Lamin Type A; EC 2.5.1.29/Farnesyltranstransferase |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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