title: CIZ1, a p21Cip1/Waf1-interacting protein, functions as a tumor suppressor in vivo.
abstract: CIZ1 is a nuclear protein involved in DNA replication and is also implicated in human diseases including cancers. To gain an insight into its function in vivo, we generated mice lacking Ciz1. Ciz1-deficient (Ciz1(-/-)) mice grew without any obvious abnormalities, and Ciz1(-/-) mouse embryonic fibroblasts (MEFs) did not show any defects in cell cycle status, cell growth, and DNA damage response. However, Ciz1(-/-) MEFs were sensitive to hydroxyurea-mediated replication stress and susceptible to oncogene-induced cellular transformation. In addition, Ciz1(-/-) mice developed various types of leukemias by retroviral insertional mutagenesis. These results indicate that CIZ1 functions as a tumor suppressor in vivo.
authors.affiliation: Department of Disease Model, Research Institute for Radiation Biology and Medicine, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan.
authors.forename: Rio
authors.initials: R
authors.lastname: Nishibe
authors.forename: Wataru
authors.initials: W
authors.lastname: Watanabe
authors.forename: Takeshi
authors.initials: T
authors.lastname: Ueda
authors.forename: Norimasa
authors.initials: N
authors.lastname: Yamasaki
authors.forename: Richard
authors.initials: R
authors.lastname: Koller
authors.forename: Linda
authors.initials: L
authors.lastname: Wolff
authors.forename: Zen-ichiro
authors.initials: Z
authors.lastname: Honda
authors.forename: Motoaki
authors.initials: M
authors.lastname: Ohtsubo
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Honda
mesh_terms: D000818:Animals; D064007:Ataxia Telangiectasia Mutated Proteins; D002453:Cell Cycle / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004622:Embryo, Mammalian / Q000166:cytology; D005347:Fibroblasts / Q000378:metabolism / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology
chemical_list: C493957:Cdkn1a protein, mouse; D018797:Cell Cycle Proteins; C540084:Ciz1 protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; C576325:Atm protein, mouse; D017346:Protein Serine-Threonine Kinases