Chromosome 12 Open Reading Frame 5 (C12orf5), also known as TP53-induced glycolysis and apoptosis regulator (TIGAR), is a gene located on chromosome 12 in humans. This gene plays a crucial role in cellular metabolism and apoptosis, making it a significant subject of study in the fields of cancer research and cellular biology.
The expression of C12orf5 is regulated by various factors, including the tumor suppressor protein p53. Under conditions of cellular stress, such as DNA damage, p53 activates the transcription of C12orf5. This activation leads to the production of the TIGAR protein, which plays a role in regulating glycolysis and protecting cells from oxidative stress .
The TIGAR protein encoded by C12orf5 functions as a fructose-2,6-bisphosphatase. By decreasing the levels of fructose-2,6-bisphosphate, TIGAR reduces glycolysis and redirects glucose metabolism towards the pentose phosphate pathway. This shift helps in the generation of NADPH, which is crucial for combating oxidative stress and maintaining cellular redox balance .
Additionally, TIGAR has been implicated in the regulation of apoptosis. By modulating the levels of reactive oxygen species (ROS) within the cell, TIGAR can influence cell survival and death pathways. This dual role in metabolism and apoptosis makes TIGAR a key player in cellular homeostasis .
Given its role in regulating glycolysis and apoptosis, C12orf5/TIGAR has garnered significant attention in cancer research. Overexpression of TIGAR has been observed in various types of cancers, where it contributes to tumor growth and survival by protecting cancer cells from oxidative stress. Conversely, downregulation of TIGAR can sensitize cancer cells to chemotherapy and radiation therapy, making it a potential target for cancer treatment .