An autonomous institute of the Agency for Science, Technology and Research in Singapore has announced the discovery of a human protein called Bax-beta (Baxá), which can potentially cause the death of cancer cells and lead to new approaches in cancer treatment.
"Our research findings reveal that Baxá protein levels are normally kept at essentially undetectable levels in healthy cells by the protein degradation machine in cells known as proteasomes," said Dr. Victor Yu, who led the Institute of Molecular and Cell Biology (IMCB) research team.
In a researcher article in the journal Molecular Cell, the researchers describe proteasomes as "protein-digesting machines" that regulate cellular levels of various proteins, including that of the lethal Baxá, by breaking them into smaller components within the cell.
"Thus, the proteasomes are there to keep the lethal Baxá in check. This is exciting - if the proteasome-mediated degradation of Baxá could be inhibited specifically in cancer cells, it could cause the harmful cancer cells to go through apoptosis," Dr. Victor Yu said.
In apoptosis, unwanted, damaged and infected cells are eliminated.
Before the discovery of Baxá, only one single protein called Bax-alpha (Baxa) had been extensively studied in cells.
The researchers have now found that Baxá is able to associate with, and promote, Baxa activation, and that Baxá, in its native form, is 100 times more potent than its sibling Baxa in triggering a key step in apoptosis.
They believe that the development of such compounds as can elevate levels of Baxá, or stimulate its interaction with Baxa, may pave the way for new drug approaches to cancer treatment, as these compounds are likely to enhance the apoptotic signals triggered by many conventional cancer drugs, which frequently cause toxic side effects in patients when higher doses of drugs are needed.
Dr. David Andrews, Professor of Biochemistry and Biomedical Sciences at McMaster University, Canada said: "The beta-isoform4 of Bax has been enigmatic for several years. Although earlier research had hinted at its existence, the protein has proven extremely difficult to detect or examine functionally. Even attempts to produce the protein in the laboratory have been largely unsuccessful. In this study the Yu group resolves these issues by demonstrating that in cells Baxá is normally rapidly degraded and kept at low levels, and when it is not degraded, it is profoundly apoptotic on its own and works in concert with Baxa. These studies provide information necessary for the elucidation of the importance of Baxá in cell physiology."