Anti-anti-oncogene: Trim24 vs p53
A new opponent of the "keeper of the genome", the p53 protein, has been discoveredDmitry Safin, Compulenta
A group of scientists from the USA found out that the Trim24 protein can contribute to the destruction of p53, the most important protein that regulates the cell cycle and triggers the mechanism of apoptosis (programmed cell death).
One of the main functions of the p53 protein is, therefore, to suspend the replication of potentially oncogenic cells. Violations of the action of p53 are observed in half of the diagnosed cases of cancer.
Trim24, as the researchers demonstrated, affects p53 by attaching the ubiquitin protein to it. The p53 marked in this way is destroyed under the influence of specialized protein complexes – proteasomes.
The research methodology chosen by scientists is quite unusual: it is known that in most works devoted to the p53 gene and protein, violations of their functioning in tumor cells are analyzed. "We decided to isolate p53 from healthy cells and carefully consider the mechanisms of its regulation," explains team leader Michelle Barton from the Cancer Research Center at the University of Texas. A new laboratory line of mice was obtained in which a biochemical label was attached to the expressed protein p53; after making sure that the protein was "normal", the scientists extracted it using this label. "Then, using mass spectrometry methods, we determined which proteins interact with p53," says Ms. Barton.
Experiments with the created samples showed that suppression of Trim24 functions leads to an increase in the level of p53 expression in the cell nucleus, and vice versa; when cells were treated with a substance that inhibits the action of proteasomes, the level of p53 expression also increased. At the same time, a violation of Trim24 expression in breast, lung, colon and prostate cancer cells triggered the process of apoptosis.
The bonus protein, a "simplified version" of Trim24, which is expressed in the body of the fruit fly, performs, according to the authors, similar functions. The relationship between Trim24 and p53 is thus preserved during evolution.
The full version of the report will be published in the journal Proceedings of the National Academy of Sciences.
Prepared based on the materials of the Cancer Research Center at the University of Texas.
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