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J. Biol. Chem., Vol. 281, Issue 52, 40440-40449, December 29, 2006

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YB-1 Is Important for an Early Stage Embryonic Development

NEURAL TUBE FORMATION AND CELL PROLIFERATION^*

Takeshi Uchiumi¹, Abbas Fotovati, Takakazu Sasaguri^¶, Kohtaro Shibahara^||, Tatsuo Shimada^**, Takao Fukuda^||, Takanori Nakamura^||, Hiroto Izumi, Teruhisa Tsuzuki, Michihiko Kuwano, and Kimitoshi Kohno

From the Department of Molecular Biology, University of Occupational and Environmental Health, School of Medicine, Yahatanishi-ku, Kitakyushu 807-8555, Research Center for Innovative Cancer Therapy, Kurume University, Kurume, Fukuoka 830-0011, the ^¶Department of Pathology II, University of Occupational and Environmental Health, School of Medicine, Yahatanishi-ku, Kitakyushu 807-8555, the ^||Department of Medical Biochemistry, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, ^**Health Sciences, School of Nursing, Faculty of Medicine, Oita University, Yufushi 879-5595, and Medical Biophysics and Radiation Biology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan

The eukaryotic Y-box-binding protein-1 (YB-1) is involved in the transcriptional and translational control of many biological processes, including cell proliferation. In clinical studies, the cellular level of YB-1 closely correlates with tumor growth and prognosis. To understand the role of YB-1 in vivo, especially in the developmental process, we generated YB-1 knock-out mice, which are embryonic lethal and exhibit exencephaly associated with abnormal patterns of cell proliferation within the neuroepithelium. -Actin expression and F-actin formation were reduced in the YB-1 null embryo and YB-1^-/- mouse embryonic fibroblasts, suggesting that the neural tube defect is caused by abnormal cell morphology and actin assembly within the neuroepithelium. Fibroblasts derived from YB-1^-/- embryos demonstrated reduced growth and cell density. A colony formation assay showed that YB-1^-/- mouse embryonic fibroblasts failed to undergo morphological transformation and remained contact-inhibited in culture. These results demonstrate that YB-1 is involved in early mouse development, including neural tube closure and cell proliferation.

Received for publication, June 21, 2006 , and in revised form, October 13, 2006.

^* This work was supported by a grant-in-aid for scientific research on the priority area of ABC proteins, Core Research for Evolutional Science and Technology (CREST) of the Japan Science and Technology Corp. (JST), the second-term comprehensive 10-year strategy for cancer control from the Ministry of Health and Welfare of Japan, and the Cancer Research fund from Ministry of Education, Culture, Sports, Science, and Technology, Japan. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Experimental Procedures and Figs. S1 and S2.

¹ To whom correspondence should be addressed. Tel.: 81-93-691-7423; Fax: 81-93-692-6233; E-mail: uchiumi{at}med.uoeh-u.ac.jp.

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