Isolation and characterization of the TIGA genes, whose transcripts are induced by growth arrest.
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.
Yabuta
Norikazu
N
Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka 567-0871, Japan.
Onda
Hiroaki
H
Watanabe
Masafumi
M
Yoshioka
Naohisa
N
Nagamori
Ippei
I
Funatsu
Tomoyuki
T
Toji
Shingo
S
Tamai
Katsuyuki
K
Nojima
Hiroshi
H
D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003260:Contact Inhibition; D016895:Culture Media, Serum-Free; D016147:Genes, Tumor Suppressor; D006801:Humans; D007700:Kinetics; D019656:Loss of Heterozygosity; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D026901:Membrane Transport Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D033681:Mitochondrial Membrane Transport Proteins; D024101:Mitochondrial Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000235:genetics; D017434:Protein Structure, Tertiary; D062085:RNA, Long Noncoding; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000378:metabolism; D016192:Resting Phase, Cell Cycle / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D014410:Tumor Stem Cell Assay; D015854:Up-Regulation
D016895:Culture Media, Serum-Free; C514590:EPB41L4A-AS1 lncRNA, human; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D033681:Mitochondrial Membrane Transport Proteins; D024101:Mitochondrial Proteins; D062085:RNA, Long Noncoding; D012333:RNA, Messenger