| The transcription factor Sp1 is responsible for aging dependent altered nucleocytoplasmic trafficking. | |
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MedLine Citation:
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PMID: 23013401 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Hyporesponsiveness to external signals, such as growth factors and apoptotic stimuli, is a cardinal feature of cellular senescence. We previously reported that an aging-dependent marked reduction in nucleocytoplasmic trafficking related (NCT) genes could be responsible for this phenomenon. In searching for the mechanism, we identified the transcription factor, Sp1, as a common regulator of NCT genes, including various nucleoporins, importins, exportins and Ran GTPase cycle-related genes. Sp1 knockdown led to a reduction of those genes in young human diploid fibroblast cells (HDF); Sp1 overexpression induced those genes in senescent cells. In addition, epidermal growth factor stimulation-induced p-ERK1/2 nuclear translocation and Elk-1 phosphorylation were severely impaired by Sp1 depletion in young HDFs; Sp1 overexpression restored the nuclear translocation of p-ERK1/2 in senescent HDFs. Furthermore, we observed that Sp1 protein levels were decreased in senescent cells, and H(2) O(2) treatment decreased Sp1 levels in a proteasome-dependent manner. In addition, O-GlcNAcylation of Sp1 was decreased in senescent cells as well as in H(2) O(2) -treated cells. Taken together, these results suggest that Sp1 could be a key regulator in the control of NCT genes and that reactive oxygen species-mediated alteration in Sp1 stability may be responsible for the generalized repression of those genes, leading to formation of the senescence-dependent functional nuclear barrier, resulting in subsequent hyporesponsiveness to external signals. © 2012 The Authors Aging Cell © 2012 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland. |
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Authors:
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Sung Young Kim; Hyun Tae Kang; Jeong A Han; Sang Chul Park |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-9-27 |
Journal Detail:
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Title: Aging cell Volume: - ISSN: 1474-9726 ISO Abbreviation: Aging Cell Publication Date: 2012 Sep |
Date Detail:
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Created Date: 2012-9-27 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101130839 Medline TA: Aging Cell Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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© 2012 The Authors Aging Cell © 2012 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland. |
Affiliation:
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Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon, 406-840, South Korea. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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