CIZ1, a p21Cip1/Waf1-interacting protein, functions as a tumor suppressor in vivo

• Published in: FEBS letters 2013-05, Vol.587 (10), p.1529-1535
• Main Authors: Nishibe, Rio, Watanabe, Wataru, Ueda, Takeshi, Yamasaki, Norimasa, Koller, Richard, Wolff, Linda, Honda, Zen-ichiro, Ohtsubo, Motoaki, Honda, Hiroaki
• Format: Article
• Language: English
• Subjects: Animals; Ataxia Telangiectasia Mutated Proteins; Cell Cycle - genetics; Cell Cycle Proteins - genetics; Cell Cycle Proteins - metabolism; Cell Proliferation; Cell Transformation, Neoplastic - genetics; Cell Transformation, Neoplastic - metabolism; Cells, Cultured; CIZ1 (Cip1 interacting zinc finger protein 1); Cyclin-Dependent Kinase Inhibitor p21 - metabolism; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Embryo, Mammalian - cytology; Fibroblasts - metabolism; Fibroblasts - physiology; Mice; Mice, Knockout; Models, Biological; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Nuclear Proteins - physiology; p21Cip1/Waf1; Protein Binding; Protein-Serine-Threonine Kinases - genetics; Protein-Serine-Threonine Kinases - metabolism; Tumor Suppressor Proteins - genetics; Tumor Suppressor Proteins - metabolism; Tumor Suppressor Proteins - physiology; Tumorigenesis
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/j.febslet.2013.03.034

•Ciz1-deficient (Ciz1−/−) mouse embryonic fibroblasts (MEFs) did not show defects in cell cycle status, cell growth, and DNA damage response.•Ciz1−/− MEFs were sensitive to replication stress and susceptible to cellular transformation.•Ciz1−/− mice developed leukemias by retroviral insertional mutagenesis.•CIZ1 functions as a tumor suppressor in vivo. 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.