An antibody showed the ability to bind to the protein Bak and cause apoptosis.
Researchers in a recent study found a novel method that activated the protein Bak and triggered cancer cell death.
Bak is critical for apoptosis, the process that removes unneeded cells. Bak is in an inert state in healthy cells, but can transform into a killer protein to destroy the cell that received the signal to die. In the study, published in Nature Communications, researchers discovered an antibody they produced was able to bind to Bak and trigger its activation.
"We were excited when we realised we had found an entirely new way of activating Bak," said researcher Ruth Kluck, BSc, PhD, QLD. "There is great interest in developing drugs that trigger Bak activation to treat diseases such as cancer where apoptosis has gone awry. This discovery gives us a new starting point for developing therapies that directly activate Bak and cause cell death."
Researchers then analyzed information about Bak’s 3-dimensional structure, and were able to discover how the antibody was able to activate the protein.
"It is well known that Bak can be activated by a class of proteins called 'BH3-only proteins' that bind to a groove on Bak,” Dr Kluck said. “We were surprised to find that despite our antibody binding to a completely different site on Bak, it could still trigger activation."
Researchers believe drugs that target the activation site could be an effective addition to treatments that mimic BH3-only proteins. They are currently working on developing the antibody into a drug.
"The advantage of our antibody is that it can't be 'mopped up' and neutralized by pro-survival proteins in the cell, potentially reducing the chance of drug resistance occurring," Dr Kluck concluded.