Surpassed only by cardiovascular diseases that kill 16% of all who pass away in an average year, cancer is the second leading cause of morality around the world, accounting for an estimated 10 million – or one in six – fatalities. 

Thus it is no surprise that scientists are desperately trying to develop new drugs that can better treat oncological disease. In a world first, a team of researchers from Ben-Gurion University (BGU) of the Negev in Beersheba scientists have discovered the biological function of a naturally occurring peptide (a short chains of amino acids linked by peptide bond) as a protein kinase inhibitor. That discovery could lead to a class of better cancer drugs.

Their findings were published in the prestigious peer-reviewed journal PNAS (Proceedings of the US National Academy of Sciences) under the title “Unraveling the hidden role of a uORF-encoded peptide as a kinase inhibitor of PKCs.” 

As scientists discover more about the importance of messenger RNA (mRNA) – a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene and is read by a ribosome in the process of synthesizing a protein – new fields of inquiry arise. In general, each of the mRNA in our body codes for a major protein with unique functions. Recently, bioinformatics showed that, in addition, about 40% of mRNAs contain sequences that may code for short peptides in a region that was previously considered as “non-coding.”  But, unlike the functional proteins translated from the mRNAs, it was not clear if the short peptides had a function.

Now, Prof. Etta Livneh and her colleagues have isolated and proven the role of a single short peptide; it serves as a kinase inhibitor. Through mouse models and human cells, she and her colleagues demonstrated that this peptide inhibits cancer cell survival, tumor progression, invasion, and metastasis.

Proteins (especially protein kinases) propagate signals in cells dictating their fate (humans have more than 500 human kinases). Their inhibitors block the kinase enzyme that carries instructions to the cell. For example, if the kinase instructs a cancer cell to divide and reproduce, inhibiting the kinase would slow down the spread of cancer cells.

“Clearly demonstrating the role of this peptide is just the tip of the iceberg,” said Livneh about her groundbreaking discovery on which she and her team worked for a decade. “Now that we know that at least some peptides have a biological function, we can begin to discover the roles of many more.”

In an interesting twist, when the gene from which this peptide originates was grouped into a family for classification, it was given the Greek letter Eta – which just so happens to be Livneh’s first name.

Livneh is a member of the department of immunology, microbiology and genetics at BGU’s Faculty of Health Sciences. She collaborated with Prof. Esti Yeger-Lotem from the department of clinical biochemistry and pharmacology and Prof. Moshe Elkabets in the Faculty of Health Sciences and other BGU researchers from the departments of life sciences and computer sciences in the Faculty of Natural Sciences.

Additional researchers include Divya Ram Jayaram, Sigal Frost, Chanan Argov, Vijayasteltar Belsamma Liju, Nikhil Ponnoor Anto, Amitha Muraleedharan, Assaf Ben-Ari, Rose Sinay, Ilan Smoly, Ofra Novoplansky, Noah Isakov, Dr. Debra Toiber and Chen Keasar.