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Nucleic Acids Research Advance Access published online on September 14, 2006
Nucleic Acids Research, doi:10.1093/nar/gkl651
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© 2006 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Molecular Biology

Isolation and characterization of the TIGA genes, whose transcripts are induced by growth arrest

Norikazu Yabuta1, Hiroaki Onda1, Masafumi Watanabe1,2, Naohisa Yoshioka1, Ippei Nagamori1, Tomoyuki Funatsu1, Shingo Toji2, Katsuyuki Tamai2 and Hiroshi Nojima1,*

1 Research Institute for Microbial Diseases, Osaka University 3-1 Yamadaoka, Suita, Osaka 567-0871, Japan 2 Ina Laboratory, MBL Co. Ltd. 1063-103 Ohara, Terasawaoka, Ina, Nagano 396-0002, Japan

*To whom correspondence should be addressed. Tel: +81 6 6875 3980; Fax: +81 6 6875 5192; Email: snj-0212{at}biken.osaka-u.ac.jp

Received August 12, 2006. Revised August 12, 2006. Accepted August 24, 2006.

We report here the isolation of 44 genes that are upregulated after serum starvation and/or contact inhibition. These genes have been termed TIGA, after Transcript Induced by Growth Arrest. We found that there are two kinds of G0 phases caused by serum starvation, namely, the shallow G0 (or G0/G1) and the deep G0 phases. The shallow G0 is induced by only a few hours of serum starvation, while deep G0 is generated after 3 days of serum starvation. We propose that mammalian cells enter deep G0 through a G0 gate, which is only opened on the third day of serum starvation. TIGA1, one of the uncharacterized TIGA genes, encodes a homolog of cyanate permease of bacteria and localizes in mitochondria. This suggests that Tiga1 is involved in the inorganic ion transport and metabolism needed to maintain the deep G0 phase. Ectopic expression of TIGA1 inhibited not only tumor cell proliferation but also anchorage-independent growth of cancer cell lines. A microsatellite marker, ENDL-1, allowed us to detect loss of heterozygosity around the TIGA1 gene region (5q21–22). Further analysis of the TIGA genes we have identified here may help us to better understand the mechanisms that regulate the G0 phase.

Present address: Naohisa Yoshioka, Howard Hughes Medical Institute, Department of Cellular and Molecular Medicine, UCSD School Medicine, 9500 Gilman Drive, La Jolla, CA 92093-0686, USA


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