title: The role of nuclear lamin B1 in cell proliferation and senescence.
abstract: Nuclear lamin B1 (LB1) is a major structural component of the nucleus that appears to be involved in the regulation of many nuclear functions. The results of this study demonstrate that LB1 expression in WI-38 cells decreases during cellular senescence. Premature senescence induced by oncogenic Ras also decreases LB1 expression through a retinoblastoma protein (pRb)-dependent mechanism. Silencing the expression of LB1 slows cell proliferation and induces premature senescence in WI-38 cells. The effects of LB1 silencing on proliferation require the activation of p53, but not pRb. However, the induction of premature senescence requires both p53 and pRb. The proliferation defects induced by silencing LB1 are accompanied by a p53-dependent reduction in mitochondrial reactive oxygen species (ROS), which can be rescued by growth under hypoxic conditions. In contrast to the effects of LB1 silencing, overexpression of LB1 increases the proliferation rate and delays the onset of senescence of WI-38 cells. This overexpression eventually leads to cell cycle arrest at the G1/S boundary. These results demonstrate the importance of LB1 in regulating the proliferation and senescence of human diploid cells through a ROS signaling pathway.
authors.affiliation: Department of Cell and Molecular Biology, Division of Pulmonary and Critical Care Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Shimi
authors.forename: Veronika
authors.initials: V
authors.lastname: Butin-Israeli
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Adam
authors.forename: Robert B
authors.initials: RB
authors.lastname: Hamanaka
authors.forename: Anne E
authors.initials: AE
authors.lastname: Goldman
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Lucas
authors.forename: Dale K
authors.initials: DK
authors.lastname: Shumaker
authors.forename: Steven T
authors.initials: ST
authors.lastname: Kosak
authors.forename: Navdeep S
authors.initials: NS
authors.lastname: Chandel
authors.forename: Robert D
authors.initials: RD
authors.lastname: Goldman
mesh_terms: D002453:Cell Cycle / Q000235:genetics; D002460:Cell Line; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation; D016922:Cellular Senescence / Q000235:genetics; D003598:Cytoskeletal Proteins / Q000235:genetics* / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D020868:Gene Silencing; D006801:Humans; D017382:Reactive Oxygen Species / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000378:metabolism; D015398:Signal Transduction; D016615:Telomere / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D018631:ras Proteins / Q000378:metabolism
chemical_list: C114988:CKAP2 protein, human; D003598:Cytoskeletal Proteins; D017382:Reactive Oxygen Species; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53; D018631:ras Proteins