title: Ribosomal L1 domain and lysine-rich region are essential for CSIG/ RSL1D1 to regulate proliferation and senescence.
abstract: The expression change of cellular senescence-associated genes is underlying the genetic foundation of cellular senescence. Using a suppressive subtractive hybridization system, we identified CSIG (cellular senescence-inhibited gene protein; RSL1D1) as a novel senescence-associated gene. CSIG is implicated in various process including cell cycle regulation, apoptosis, and tumor metastasis. We previously showed that CSIG plays an important role in regulating cell proliferation and cellular senescence progression through inhibiting PTEN, however, which domain or region of CSIG contributes to this function? To clarify this question, we investigated the functional importance of ribosomal L1 domain and lysine (Lys) -rich region of CSIG. The data showed that expression of CSIG potently reduced PTEN expression, increased cell proliferation rates, and reduced the senescent phenotype (lower SA-β-gal activity). By contrast, neither the expression of CSIG N- terminal (NT) fragment containing the ribosomal L1 domain nor C-terminal (CT) fragment containing Lys-rich region could significantly altered the levels of PTEN; instead of promoting cell proliferation and delaying cellular senescence, expression of CSIG-NT or CSIG-CT inhibited cell proliferation and accelerated cell senescence (increased SA-β-gal activity) compared to either CSIG over-expressing or control (empty vector transfected) cells. The further immunofluorescence analysis showed that CSIG-CT and CSIG-NT truncated proteins exhibited different subcellular distribution with that of wild-type CSIG. Conclusively, both ribosomal L1 domain and Lys-rich region of CSIG are critical for CSIG to act as a regulator of cell proliferation and cellular senescence.
authors.affiliation: Research Center on Aging, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, 38 Xueyuan Road, Beijing 100191, PR China.
authors.forename: Liwei
authors.initials: L
authors.lastname: Ma
authors.affiliation: Research Center on Aging, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, 38 Xueyuan Road, Beijing 100191, PR China.
authors.forename: Wenting
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Research Center on Aging, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, 38 Xueyuan Road, Beijing 100191, PR China.
authors.forename: Quanhui
authors.initials: Q
authors.lastname: Zheng
authors.affiliation: Research Center on Aging, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, 38 Xueyuan Road, Beijing 100191, PR China.
authors.forename: Tianda
authors.initials: T
authors.lastname: Chen
authors.affiliation: Research Center on Aging, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, 38 Xueyuan Road, Beijing 100191, PR China.
authors.forename: Ji
authors.initials: J
authors.lastname: Qi
authors.affiliation: Research Center on Aging, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, 38 Xueyuan Road, Beijing 100191, PR China.
authors.forename: Guodong
authors.initials: G
authors.lastname: Li
authors.affiliation: Research Center on Aging, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, 38 Xueyuan Road, Beijing 100191, PR China. Electronic address: tztong@bjmu.edu.cn.
authors.forename: Tanjun
authors.initials: T
authors.lastname: Tong
mesh_terms: D000818:Animals; D019556:COS Cells; D049109:Cell Proliferation / Q000502:physiology*; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000502:physiology*; D002522:Chlorocebus aethiops; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D008239:Lysine / Q000737:chemistry / Q000378:metabolism*; D011257:Pregnancy Proteins / Q000378:metabolism*; D012269:Ribosomal Proteins / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D013347:Subcellular Fractions / Q000378:metabolism
chemical_list: D011257:Pregnancy Proteins; C117409:RSL1D1 protein, human; D012269:Ribosomal Proteins; D008239:Lysine
keywords: CSIG/RSL1D1; Cellular senescence; Lysine-rich region; Proliferation; Ribosomal L1 domain