The identification and characterization of a new GTP-binding protein (Gbp45) involved in cell proliferation and death related to mitochondrial function.
We describe the identification and characterization of a GTP-binding protein with a molecular weight of 45 kD (Gbp45). Gbp45 cDNA was found to overlap with a hypothetical human protein, PTD004, the sequence of which was previously deposited in the databases. The gene for PTD004 was recently found to be one of the ATPases, hOLA1 (human Obg-like ATPase 1). The Gbp45 gene encodes a protein of 396 amino acid residues. Immunocytochemical analysis and examination with GFP-tagged protein revealed that Gbp45 is primarily located in the cytosolic compartment. Immunoblot analysis showed that the Gbp45 protein is strongly expressed in the neuronal tissues and pancreas. T43N and T56N mutations resulted in a loss of Gbp45's ability to bind to GTP and a loss of GTPase activity. In cultured cells, the transfection of wild-type Gbp45 accelerated cell proliferation, though T43N and T56N mutations induced cell death. Down-regulating Gbp45 expression decreased the cell proliferation rate and increased the rate of cell death induced by the inhibition of mitochondrial electron transport. These findings indicate that Gbp45 plays important roles in cell proliferation and death related to mitochondrial function.
Kira
Yukimi
Y
Department of Central Laboratory, Osaka City University Medical School, Osaka, 545-8585, Japan.
Nishikawa
Manabu
M
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D016923:Cell Death / Q000502:physiology*; D002460:Cell Line; D049109:Cell Proliferation; D005260:Female; D019204:GTP-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006160:Guanosine Triphosphate / Q000031:analogs & derivatives / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000378:metabolism*; D008969:Molecular Sequence Data; D008970:Molecular Weight; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution
D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins; D006160:Guanosine Triphosphate; D019204:GTP-Binding Proteins; C534031:Gbp45 protein, human