| Limited capacity of the nuclear matrix to bind telomere repeat binding factor TRF1 may restrict the proliferation of mortal human fibroblasts. | |
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MedLine Citation:
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PMID: 14681297 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The maintenance of telomere integrity is essential for prolonged cell proliferation, and failure in this mechanism is a most consistent manifestation of cellular senescence. In this study, we investigated the role of telomere repeat binding factor (TRF1) in the proliferation of human fibroblasts. TRF1 expression is upregulated in a large variety of immortal human cells and supports de novo telomere formation in a dose-dependent manner. These observations suggest that the suppression of TRF1 might limit telomere maintenance and thus the life span of mortal cells. However, primary fibroblasts ectopically overexpressing TRF1 were unable to avoid senescence. On the other hand, exogenously expressed TRF1 in primary fibroblasts neither supported de novo telomere formation nor bound to the nuclear matrix as tightly as observed in immortal cells that show upregulated TRF1 expression. We present evidence suggesting that mortal human cells lack specific ligand(s) that anchor TRF1 to the nuclear matrix and that this contributes to their limited lifespan. |
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Authors:
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Jun Okabe; Akiko Eguchi; Renu Wadhwa; Randeep Rakwal; Rumi Tsukinoki; Takao Hayakawa; Mahito Nakanishi |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2003-12-17 |
Journal Detail:
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Title: Human molecular genetics Volume: 13 ISSN: 0964-6906 ISO Abbreviation: Hum. Mol. Genet. Publication Date: 2004 Feb |
Date Detail:
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Created Date: 2004-01-16 Completed Date: 2004-09-08 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 9208958 Medline TA: Hum Mol Genet Country: England |
Other Details:
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Languages: eng Pagination: 285-93 Citation Subset: IM |
Affiliation:
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Gene Function Research Center, National Institute of Advanced Industrial Science and Technology, 1-1-1 Higashi, Tsukuba, Ibaraki 305-8562, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Cell Division
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physiology Fibroblasts / cytology, metabolism* Humans Nuclear Matrix / metabolism* Telomere / metabolism Telomeric Repeat Binding Protein 1 / metabolism* Up-Regulation |
| Chemical | |
Reg. No./Substance:
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0/Telomeric Repeat Binding Protein 1 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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