A team of researchers from the Perelman School of Medicine, University of Pennsylvania, has identified a class of p53 target genes and regulatory molecules that represent more promising therapeutic candidates. Researchers describes that, p53 participates in a molecular feedback circuit with malic enzymes, thereby showing that p53 activity is also involved in regulating metabolism.(The Yang lab identified p53's role in glucose metabolism in the past.)
The new findings, Yang (lead researcher) says, suggest that p53 acts as a molecular sensor of metabolic stress and explains how metabolic stress can lead to senescence in cells.
"We uncovered an important regulatory mechanism for p53 as well as an effector mechanism for p53," Yang says.
Significantly, the findings also identify malic enzymes as novel and potentially useful pharmaceutical targets for anticancer therapy, as well as possible mediators of the normal aging process though neither possibility was actually addressed in the current study.
As cells become damaged and precancerous, the p53 protein prevents those cells from continuing towards becoming tumors by causing the cells to senesce. Metabolic cues also regulate senescence, but the molecular relays coupling those two processes, senescence and metabolism remained unknown................
