title: p41-Arc, a regulatory subunit of Arp2/3 complex, can induce premature senescence in the absence of p53 and Rb.
abstract: Cellular senescence is a tumor-suppressive process instigated by proliferation in the absence of telomere replication, by cellular stresses such as oncogene activation, or by activation of the tumor suppressor proteins, such as Rb or p53. This process is characterized by an irreversible cell cycle exit, a unique morphology, and expression of senescence-associated-β-galactosidase (SA-β-gal). Despite the potential biological importance of cellular senescence, little is known of the mechanisms leading to the senescent phenotype. p41-Arc has been known to be a putative regulatory component of the mammalian Arp2/3 complex, which is required for the formation of branched networks of actin filaments at the cell cortex. In this study, we demonstrate that p41-Arc can induce senescent phenotypes when it is overexpressed in human tumor cell line, SaOs-2, which is deficient in p53 and Rb tumor suppressor genes, implying that p41 can induce senescence in a p53-independent way. p41-Arc overexpression causes a change in actin filaments, accumulating actin filaments in nuclei. Therefore, these results imply that a change in actin filament can trigger an intrinsic senescence program in the absence of p53 and Rb tumor suppressor genes.
authors.affiliation: Department of Microbiology Dankook University College of Medicine Cheonan, Korea. dreamer@dku.edu
authors.forename: Un Jung
authors.initials: UJ
authors.lastname: Yun
authors.forename: Sang Eun
authors.initials: SE
authors.lastname: Park
authors.forename: Deug Y
authors.initials: DY
authors.lastname: Shin
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D051376:Actin-Related Protein 2-3 Complex / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D016922:Cellular Senescence; D005347:Fibroblasts / Q000502:physiology; D006801:Humans; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism*; D016160:Retinoblastoma Protein / Q000172:deficiency* / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency* / Q000235:genetics
chemical_list: C460821:ARPC1B protein, human; D051376:Actin-Related Protein 2-3 Complex; D018797:Cell Cycle Proteins; D011994:Recombinant Proteins; D016160:Retinoblastoma Protein; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53