title: Transcription factor Sp1 prevents TRF2(ΔBΔM)-induced premature senescence in human diploid fibroblasts.
abstract: Telomere uncapping is thought to be the fundamental cause of replicative cellular senescence, but the cellular machineries mediating this process have not been fully understood. In the present study, we present the role of Sp1 transcription factor in the state of telomere uncapping using the TRF2(ΔBΔM)-induced senescence model in human diploid fibroblasts. We observed that the expression of Sp1 is down-regulated in the TRF2(ΔBΔM)-induced senescence, which was mediated by ATM and p38 MAPK. In addition, overexpression of Sp1 prevented the TRF2(ΔBΔM)-induced senescence. Among transcriptional targets of Sp1, expression levels of nuclear transport genes such as karyopherin α, Nup107, and Nup50 were down-regulated in the TRF2(ΔBΔM)-induced senescence, which was prevented by Sp1 overexpression. Moreover, inhibition of the nuclear transport by wheat germ agglutinin (an import inhibitor) and leptomycin B (an export inhibitor) induced premature senescence. These results suggest that Sp1 is an anti-senescence transcription factor in the telomere uncapping-induced senescence and that down-regulation of Sp1 leads to the senescence via down-regulation of the nuclear transport.
authors.affiliation: Department of Biochemistry and Molecular Biology, Kangwon National University School of Medicine, Chuncheon, 200-701, South Korea.
authors.forename: Hyun Ju
authors.initials: HJ
authors.lastname: An
authors.affiliation: Department of Biochemistry and Molecular Biology, Kangwon National University School of Medicine, Chuncheon, 200-701, South Korea.
authors.forename: Hyeon Ju
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Department of Biomedical Science, Graduate School of Biomedical Science & Engineering, Hanyang University, Seoul, 133-791, South Korea.
authors.forename: Suhwa
authors.initials: S
authors.lastname: Jang
authors.affiliation: Department of Biological Sciences, College of Natural Sciences, Kangwon National University, Chuncheon, 200-701, South Korea.
authors.forename: Yu-Jin
authors.initials: YJ
authors.lastname: Jung
authors.affiliation: Department of Medical Biotechnology, College of Biomedical Science, Institute of Bioscience & Biotechnology, Kangwon National University, Chuncheon, 200-701, South Korea.
authors.forename: Sun Shim
authors.initials: SS
authors.lastname: Choi
authors.affiliation: Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon, 406-840, South Korea.
authors.forename: Sang Chul
authors.initials: SC
authors.lastname: Park
authors.affiliation: Department of Biochemistry and Molecular Biology, Kangwon National University School of Medicine, Chuncheon, 200-701, South Korea. gshja@kangwon.ac.kr.
authors.forename: Jeong A
authors.initials: JA
authors.lastname: Han
mesh_terms: D016922:Cellular Senescence / Q000502:physiology*; D004171:Diploidy; D005347:Fibroblasts / Q000166:cytology; D006801:Humans; D016329:Sp1 Transcription Factor / Q000502:physiology*; D035341:Telomeric Repeat Binding Protein 2 / Q000502:physiology*
chemical_list: D016329:Sp1 Transcription Factor; C504753:TERF2 protein, human; D035341:Telomeric Repeat Binding Protein 2
keywords: Nuclear transport; Senescence; Sp1; TRF2ΔBΔM; Telomere uncapping