| Progeria, the nucleolus and farnesyltransferase inhibitors. | |
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MedLine Citation:
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PMID: 20074076 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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HGPS (Hutchinson-Gilford progeria syndrome) is a rare genetic disease affecting children causing them to age and die prematurely. The disease is typically due to a point mutation in the coding sequence for the nuclear intermediate-type filament protein lamin A and gives rise to a dominant-negative splice variant named progerin. Accumulation of progerin within nuclei causes disruption to nuclear structure, causes and premature replicative senescence and increases apoptosis. Now it appears that accumulation of progerin may have more widespread effects than previously thought since the demonstration that the presence and distribution of some nucleolar proteins are also adversely affected in progeria cells. One of the major breakthroughs both in the lamin field and for this syndrome is that many of the cellular defects observed in HGPS patient cells and model systems can be restored after treatment with a class of compounds known as FTIs (farnesyltransferase inhibitors). Indeed, it is demonstrated that FTI-277 is able to completely restore nucleolar antigen localization in treated progeria cells. This is encouraging news for the HGPS patients who are currently undergoing clinical trials with FTI treatment. |
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Authors:
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Ishita S Mehta; Joanna M Bridger; Ian R Kill |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Biochemical Society transactions Volume: 38 ISSN: 1470-8752 ISO Abbreviation: Biochem. Soc. Trans. Publication Date: 2010 Feb |
Date Detail:
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Created Date: 2010-01-15 Completed Date: 2010-03-15 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7506897 Medline TA: Biochem Soc Trans Country: England |
Other Details:
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Languages: eng Pagination: 287-91 Citation Subset: IM |
Affiliation:
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Laboratory of Nuclear and Genomic Health, Centre for Cell and Chromosome Biology, Division of Biosciences, School of Health Sciences and Social Care, Brunel University, Uxbridge UB8 3PH, UK. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Cell Nucleolus
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metabolism* Child Chromosomal Proteins, Non-Histone / genetics, metabolism Clinical Trials as Topic Enzyme Inhibitors / therapeutic use* Farnesyltranstransferase / antagonists & inhibitors*, genetics, metabolism Humans Lamin Type A / genetics, metabolism Methionine / analogs & derivatives*, therapeutic use Progeria / drug therapy*, genetics*, metabolism, physiopathology |
| Chemical | |
Reg. No./Substance:
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0/Chromosomal Proteins, Non-Histone; 0/Enzyme Inhibitors; 0/FTI 277; 0/Lamin Type A; 0/fibrillarin; 63-68-3/Methionine; EC 2.5.1.29/Farnesyltranstransferase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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