The transcription factor Sp1 is responsible for aging-dependent altered nucleocytoplasmic trafficking
- Authors
- Kim, Sung Y.; Kang, Hyun T.; Han, Jeong A.; Park, Sang C.
- Issue Date
- Dec-2012
- Publisher
- WILEY-BLACKWELL
- Keywords
- aging; cellular senescence; nuclear pore complex; reactive oxygen species; Sp1
- Citation
- AGING CELL, v.11, no.6, pp.1102 - 1109
- Journal Title
- AGING CELL
- Volume
- 11
- Number
- 6
- Start Page
- 1102
- End Page
- 1109
- URI
- https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/15968
- DOI
- 10.1111/acel.12012
- ISSN
- 1474-9718
- Abstract
- 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 (NCT)-related 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 stimulationinduced 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 H2O2 treatment decreased Sp1 levels in a proteasome-dependent manner. In addition, O-GlcNAcylation of Sp1 was decreased in senescent cells as well as in H2O2-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.
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