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

•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.