Scientists at the University of Southern California (USC) have identified two molecules capable of killing cancer cells.
The molecules – known as peptides – actually originate from a cancer causing virus. However, they happen to target an enzyme in cancer cells that control a highly researched tumor suppressor protein known as p53. The peptides halt production of the enzyme, causing an increase in p53 levels that kills the cancer cell.
Indeed, when a number of lab mice had their lymphoma tumors injected with both peptides, they demonstrated noticeable regression without major weight-loss or other abnormalities.
The discovery is described in the journal Nature Structural & Molecular Biology.
Herpesvirus-associated ubiquitin specific protease, or HAUSP, is an enzyme that splits the normally occurring protein ubiquitin from substrates like p53.
During normal conditions, ubiquitin attaches to a substrate, causing it to deteriorate and die.
“Given the mounting evidence that HAUSP serves as a pivotal component regulating p53 protein levels, the inhibition of HAUSP should have the benefit to fully activate p53,” said Hye-Ra Lee, Ph.D., the study’s first author and a research fellow in the Department of Molecular Microbiology & Immunology at the Keck School of Medicine of USC.
Lee and her colleagues found a tight, “belt-type” interface between HAUSP and a viral protein that causes Kaposi’s sarcoma and lymphoma by utilizing co-crystal structural analysis. The peptides resulting from this viral protein bind 200 times more strongly to HAUSP than p53, making them ideal HAUSP inhibitors.
The scientists discovered that the peptides systematically prevented HAUSP from severing ubiquitin, allowing p53 levels to rise — thus representing the possibility of new chemotherapeutic molecules that can be used for anti-cancer treatments.
There is already new research being conducted with Nouri Neamati, Ph.D., associate professor of pharmacology and pharmaceutical sciences in the USC School of Pharmacy, to find lesser molecules that imitate the peptides. Other small molecules and peptides are being tested on different forms of cancer.
“Significant advances in scientific understanding often come at the intersection of independent lines of research from different disciplines, for instance, structure and virus study. Time after time, viruses are teaching us,” said Jae Jung, Ph.D., the study’s principal investigator and chairman of the Department of Molecular Microbiology & Immunology at the Keck School of Medicine.
