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

Rio Nishibe; Wataru Watanabe; Takeshi Ueda; Norimasa Yamasaki; Richard Koller; Linda Wolff; Zen-ichiro Honda; Motoaki Ohtsubo; Hiroaki Honda

doi:10.1016/j.febslet.2013.03.034

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

FEBS Lett. 2013 May 21;587(10):1529-35. doi: 10.1016/j.febslet.2013.03.034. Epub 2013 Apr 11.

Authors

Rio Nishibe¹, Wataru Watanabe, Takeshi Ueda, Norimasa Yamasaki, Richard Koller, Linda Wolff, Zen-ichiro Honda, Motoaki Ohtsubo, Hiroaki Honda

Affiliation

¹ Department of Disease Model, Research Institute for Radiation Biology and Medicine, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan.

PMID: 23583447
DOI: 10.1016/j.febslet.2013.03.034

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

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
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*
Protein Binding
Protein Serine-Threonine Kinases / genetics
Protein Serine-Threonine Kinases / metabolism
Tumor Suppressor Proteins* / genetics
Tumor Suppressor Proteins* / metabolism
Tumor Suppressor Proteins* / physiology

Substances

Cdkn1a protein, mouse
Cell Cycle Proteins
Ciz1 protein, mouse
Cyclin-Dependent Kinase Inhibitor p21
DNA-Binding Proteins
Nuclear Proteins
Tumor Suppressor Proteins
ATM protein, human
Ataxia Telangiectasia Mutated Proteins
Atm protein, mouse
Protein Serine-Threonine Kinases