*610775
TP53-INDUCED GLYCOLYSIS AND APOPTOSIS REGULATOR

Alternative titles; symbols
TIGAR
CHROMOSOME 12 OPEN READING FRAME 5; C12ORF5

HGNC Approved Gene Symbol: C12orf5

Cytogenetic location: 12p13.32     Genomic coordinates (GRCh37): 12:4,430,358 - 4,469,193 (from NCBI)

TEXT
Description
p53 (TP53; 191170) plays a role in cellular adaptation to stress and in prevention of cancer development through interactions with a number of target genes. TIGAR is a p53-inducible protein that functions to regulate glycolysis and protect against oxidative stress (Bensaad et al., 2006).

Cloning
Using chromatin immunoprecipitation analysis, Jen and Cheung (2005) identified C12ORF5 among a group of ionizing radiation-responsive genes directly regulated by p53 in human lymphoblastoid cells.

Using microarray analysis of gene expression following p53 induction in a human osteosarcoma cell line, Bensaad et al. (2006) identified C12ORF5, which they called TIGAR, as a rapidly induced gene. The predicted 270-amino acid TIGAR protein is highly conserved in vertebrates, and it shares similarity with fructose bisphosphatases (e.g., PFKFB4; 605320). Western blot analysis showed expression of a 30-kD protein.

Gene Function
Jen and Cheung (2005) found that occupancy of the C12ORF5 promoter by p53 increased after ionizing radiation, and they identified a p53 response element within the first intron of C12ORF5. Binding by p53 was delayed in ATM (607585) -/- cells.

Bensaad et al. (2006) found that overexpression of TIGAR in mouse and human cells resulted in inhibition of glycolysis, as well as a decrease in intracellular reactive oxygen species (ROS). TIGAR selectively inhibited ROS-sensitive apoptosis in a cell type-specific manner, and it required the pentose phosphate pathway to function.

Gene Structure
Bensaad et al. (2006) determined that the TIGAR gene contains 6 potential coding exons. They identified 2 possible p53-binding sites, one upstream of the first exon and the other within the first intron.

Mapping
Bensaad et al. (2006) stated that the TIGAR gene maps to chromosome 12p13.3.

REFERENCES
1. Bensaad, K., Tsuruta, A., Selak, M. A., Vidal, M. N. C., Nakano, K., Bartrons, R., Gottlieb, E., Vousden, K. H. TIGAR, a p53-inducible regulator of glycolysis and apoptosis. Cell 126: 107-120, 2006. [PubMed: 16839880, related citations] [Full Text: Elsevier Science, Pubget]

2. Jen, K.-Y., Cheung, V. G. Identification of novel p53 target genes in ionizing radiation response. Cancer Res. 65: 7666-7673, 2005. [PubMed: 16140933, related citations] [Full Text: HighWire Press, Pubget]

Creation Date: Paul J. Converse : 2/19/2007
Edit History: mgross : 02/19/2007