Uncovering the Underlying Mechanisms of Tumor Growth

Article

Discovery may help tumor suppression on a molecular level.

In a new study, researchers discovered that the p53 tumor suppressor protein is able to control gene expression by binding to both DNA and RNA.

The protein p53 is most well-known for its ability to bind to DNA and control gene expression at the level of transcription (protein synthesis). Mutations that stop the DNA binding activity are frequently found in human cancers.

Although researchers have known that p53 harbors RNA binding capacity, it has been vastly overshadowed by its DNA binding activity.

In a study published in Oncogene, researchers were able to demonstrate that p53 suppresses the synthesis of its negative regulator MDMX, through a direct interaction between p53 and the MDMX mRNA. Furthermore, a classic p53 mutation that prevents DNA binding activity was shown to have differentiated activity towards MDMX synthesis.

Study authors noted that RNA binding is not sufficient to suppress MDMX synthesis per se, and would require an additional trans-suppressor domain of p53.

“We found mutant p53 proteins that do not bind DNA instead have an effect towards mRNA translation,” said lead researcher Robin Fåhraeus. “It has been known that p53s can promote tumor growth but it is not clear what lies behind this activity and RNA binding offers one possibility.”

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