By Ellie Teng ‘21

A prominent protein in cancer research, p53, is known for its cancer fighting abilities. p53 suppresses the initiation of tumor growth by inhibiting the cancer metabolic switch from oxidative phosphorylation to glycolysis. Glycolysis is attributed to cancer metabolism and is required for tumorigenesis, or the formation of tumors. Essentially, p53 protects the genome against mutations and prevents the mutations from being passed on. However, researchers from UC San Diego published a study that revealed the previously unknown duality of p53.

The wild-type p53 (WTp53) was found to be both tumor promoting and suppressing. The protein p53 Upregulated Modulator of Apoptosis (PUMA) is found within the mitochondria of cells. When high levels of PUMA were presented, the mitochondrial pyruvate uptake was decreased and glycolysis increased in cancer patients. This caused oxidative phosphorylation to switch to glycolysis, an alternative energy pathway that may promote cancer metabolism. PUMA functions by inhibiting the mitochondrial pyruvate uptake through disrupting the oligomerization (a chemical process that converts monomers to macromolecular complexes) and function of the mitochondrial pyruvate carrier (MPC), which is a mitochondrial membrane complex that aids in pyruvate transportation. This disrupts the normal function of the mitochondria, whose primary energy pathway is oxidative phosphorylation.

WTp53 can possibly play dominant, metabolic oncogenic roles in promoting tumorigenesis. This information can prove crucial to cancer treatment developments since current drug therapies designed to enhance the function of p53 may unintentionally be causing tumor growth. The results of this experiment may be studied more in depth in the future to modify and improve existing drug treatments involving WTp53.

References

1. J. Kim, et. al., Wild-type p53 promotes cancer metabolic switch by inducing PUMA-dependent suppression of oxidative phosphorylation. Cancer Cell 35, 191-203 (2019). doi: https://doi.org/10.1016/j.ccell.2018.12.012.  
2. Image retrieved from: https://www.pexels.com/photo/addiction-aid-bottle-capsule-356054/