title: Identification of cellular senescence-specific genes by comparative transcriptomics.
abstract: Cellular senescence is defined as permanent cell cycle arrest induced by various stresses. Although the p53 transcriptional activity is essential for senescence induction, the downstream genes that are crucial for senescence remain unsolved. Here, by using a developed experimental system in which cellular senescence or apoptosis is induced preferentially by altering concentration of etoposide, a DNA-damaging drug, we compared gene expression profiles of senescent and apoptotic cells by microarray analysis. Subtraction of the expression profile of apoptotic cells identified 20 genes upregulated specifically in senescent cells. Furthermore, 6 out of 20 genes showed p53-dependent upregulation by comparing gene expression between p53-proficient and -deficient cells. These 6 genes were also upregulated during replicative senescence of normal human diploid fibroblasts, suggesting that upregulation of these genes is a general phenomenon in senescence. Among these genes, 2 genes (PRODH and DAO) were found to be directly regulated by p53, and ectopic expression of 4 genes (PRODH, DAO, EPN3, and GPR172B) affected senescence phenotypes induced by etoposide treatment. Collectively, our results identified several proteins as novel downstream effectors of p53-mediated senescence and provided new clues for further research on the complex signalling networks underlying the induction and maintenance of senescence.
authors.affiliation: Biosignal Research Center, Kobe University, 1-1 Rokkodai-cho, Nada-ku, Kobe 657-8501, Japan.|Department of Biology, Graduate School of Science, Kobe University, 1-1 Rokkodai-cho, Nada-ku, Kobe 657-8501, Japan.
authors.forename: Taiki
authors.initials: T
authors.lastname: Nagano
authors.affiliation: Biosignal Research Center, Kobe University, 1-1 Rokkodai-cho, Nada-ku, Kobe 657-8501, Japan.|Department of Biology, Graduate School of Science, Kobe University, 1-1 Rokkodai-cho, Nada-ku, Kobe 657-8501, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Nakano
authors.affiliation: Biosignal Research Center, Kobe University, 1-1 Rokkodai-cho, Nada-ku, Kobe 657-8501, Japan.|Department of Bioresource Science, Graduate School of Agricultural Science, Kobe University, 1-1 Rokkodai-cho, Nada-ku, Kobe 657-8501, Japan.
authors.forename: Akio
authors.initials: A
authors.lastname: Nakashima
authors.affiliation: Biosignal Research Center, Kobe University, 1-1 Rokkodai-cho, Nada-ku, Kobe 657-8501, Japan.|Department of Biology, Graduate School of Science, Kobe University, 1-1 Rokkodai-cho, Nada-ku, Kobe 657-8501, Japan.
authors.forename: Kengo
authors.initials: K
authors.lastname: Onishi
authors.affiliation: Biosignal Research Center, Kobe University, 1-1 Rokkodai-cho, Nada-ku, Kobe 657-8501, Japan.|Department of Biology, Graduate School of Science, Kobe University, 1-1 Rokkodai-cho, Nada-ku, Kobe 657-8501, Japan.
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Yamao
authors.affiliation: Division of Refractory and Advanced Cancer, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Enari
authors.affiliation: Biosignal Research Center, Kobe University, 1-1 Rokkodai-cho, Nada-ku, Kobe 657-8501, Japan.|Department of Bioresource Science, Graduate School of Agricultural Science, Kobe University, 1-1 Rokkodai-cho, Nada-ku, Kobe 657-8501, Japan.
authors.forename: Ushio
authors.initials: U
authors.lastname: Kikkawa
authors.affiliation: Biosignal Research Center, Kobe University, 1-1 Rokkodai-cho, Nada-ku, Kobe 657-8501, Japan.|Department of Biology, Graduate School of Science, Kobe University, 1-1 Rokkodai-cho, Nada-ku, Kobe 657-8501, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Kamada
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D002460:Cell Line; D045744:Cell Line, Tumor; D016922:Cellular Senescence / Q000187:drug effects* / Q000235:genetics; D005047:Etoposide / Q000494:pharmacology*; D020869:Gene Expression Profiling / Q000379:methods*; D056945:Hep G2 Cells; D006801:Humans; D015151:Immunoblotting; D034622:RNA Interference; D059467:Transcriptome / Q000187:drug effects*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D016159:Tumor Suppressor Protein p53; D005047:Etoposide