Researchers make case for dominant-negative effect with TP53 mutations
A large team of researchers affiliated with several institutions in the U.S. and one in Germany has found evidence that makes a case for a dominant-negative effect with TP53 mutations. In their paper published in the journal Science, the group describes their study of such gene mutations and their work, which involved editing genes to test theorized outcomes, and what they learned. David Philip Lane with the Karolinska Institutet has published a Perspective piece in the same journal issue discussing the work, along with issues involved in reconciling the findings with those found in previous studies.
The tumor protein (TP) 53 is the most often mutated gene in human cancers. It was first identified approximately 40 years ago, and since that time, it has been very heavily studied. One of the findings of such studies was that when the gene mutates, it adds new functions to a protein that suppresses tumors. In this new effort, the researchers have in essence refuted such earlier results—they are suggesting that what really happens is that the mutations that occur exert what they describe as a “dominant-negative” effect—an effect that results in a reduction of activity of wild-type (in its natural, non-mutated form) TP53. The dominant-negative effect is defined as a circumstance in which a mutation occurs that results in a gene product adversely affecting wild-type gene products—all in the same cell.
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