Cancer, aging and p53 protein: new data
Protein p53 protects against cancer by suppressing the energy metabolism of the cell
Kirill Stasevich, CompulentaProtein p53 is so well-known that it is not even necessary to imagine it.
The amount of scientific literature on it is growing, and it still remains in the spotlight as one of the main assistants in getting rid of cancer.
At the same time, it is quite difficult to find levers of influence on p53: it serves as a target for many other regulatory proteins, and it is very difficult to understand the molecular signals that come to p53.
Studying the molecular relationship of p53 with other proteins, researchers from the Medical faculty of the University of Pennsylvania (USA) found that the anti-cancer effect of p53 can be recreated without the participation of himself. It turned out that p53 is involved in the regulation of metabolism, namely in the regulation of malate dehydrogenases, enzymes of the last stages of the Krebs cycle that break down malic acid. It happens like this: when the cellular genome gets a lot of damage, p53 prevents cancer cell degeneration, triggering "emergency" aging and death. Aging is obviously a complex process that affects the metabolism, but the specific connections between the two remained unknown for a long time.
According to researchers in the journal in Nature (Jiang et al., Reciprocal regulation of p53 and malic enzymes modulates metabolism and senescence), p53 can suppress the activity of the genes malate dehydrogenases 1 and 2. On the other hand, these enzymes suppress the activity of p53 itself: if malate dehydrogenases disappear from the cell, the cell under the action of p53 begins to age rapidly. That is, a negative feedback was found between the important transcriptional regulator p53, which monitors tumors, and important enzymes of the energy cycle: the more active one is, the more passive the other.
In animal experiments, the suppression of malate dehydrogenases reduced the size of the tumor even in the absence of p53 (and turned off p53, as is known, almost inevitably leads to the appearance of cancer). And vice versa: if these enzymes were overactive, the tumor grew faster. Obviously, p53 deprives potentially dangerous cells of energy supply, suppressing the work of the Krebs cycle. Accordingly, such a cell ceases to divide, begins to grow decrepit and eventually dies.
The researchers managed to understand how p53 affects metabolism, but it is more convenient to work with enzymes, and it is much easier to control the work of the same malate dehydrogenases than to pick up the key to p53 itself. That is, theoretically, it is possible to suppress tumor growth by the p53 method without resorting to the help of the protein itself.
Prepared based on the materials of Medical Xpress: Cancer suppressor gene links metabolism with cellular aging.
Portal "Eternal youth" http://vechnayamolodost.ru15.01.2013