When Modified, Tumor Suppressor Protein RUNX3 Goes Rogue

RUNX3, a protein that normally suppresses the formation of tumors, ends up doing the opposite when it is modified by phosphorylation.

AsianScientist (Jul. 19, 2016) – Scientists in Singapore have discovered that modifications to a protein called RUNX3 may promote cancer progression.

The study was led by Professor Yoshiaki Ito, a senior principal investigator at the Cancer Science Institute of Singapore, and the research findings have been published in Proceedings of the National Academy of Sciences.

RUNX3, a member of the Runt-related transcription factor family of proteins, typically binds to DNA to suppress tumor formation. The researchers showed that an enzyme called Aurora kinase modifies RUNX3 in a process called phosphorylation. Aurora kinase has been observed to be present at unusually high levels in some cancers.

Phosphorylation prevents the binding of RUNX3 to DNA, resulting in RUNX3 relocating to centrosomes, the part of the cell that controls the start of cell division. The relocation of RUNX3 in turn allows for uncontrolled cell division in the body, which is how tumors form.

“Our results suggest that frequent overexpression of Aurora kinase in cancer may reduce RUNX3 transcription activity, leading to cell division and formation of tumors,” said Dr. Linda Chuang, senior research scientist at CSI Singapore, who is the first author of the study.

“Understanding the molecular mechanisms underlying Aurora kinase-overexpressing tumors will help in the design of targeted and personalized cancer therapy.”

Unlike other modifications that stem from changes to RUNX3 DNA or how DNA is read, phosphorylation does not accompany any changes in the DNA, making it is undetectable at the genetic level. Given that modifications such as phosphorylation are likely to be impermanent and reversible, the clinical implications are wide-ranging, the researchers said.

The article can be found at: Chuang et al. (2016) Aurora kinase-induced phosphorylation excludes transcription factor RUNX from the chromatin to facilitate proper mitotic progression.


Source: National University of Singapore; Photo: Shutterstock.
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