University of Delaware researchers have identified a protein that acts like a bodyguard to help protect and stabilize another key protein that, when unstable, is involved in Crohn’s disease. The research points to a possible pathway for developing an effective therapy for the inflammatory bowel disease. The study, conducted by Catherine Leimkuhler Grimes, PhD, and doctoral student Vishnu Mohanan, was published recently in the Journal of Biological Chemistry.
The team focused on a protein called NOD2—nucleotide-binding oligomerization domain containing protein 2. More than 58 mutations in the NOD2 gene have been linked with various diseases, and 80% are connected specifically to Crohn’s disease, according to Grimes.
In experiments to unveil NOD2’s signaling mechanisms and where they break down, “we stumbled on a chaperone molecule,” says Mohanan, lead author of the article. The chaperone molecule was HSP70 (heat shock protein 70). It assists with the folding of proteins into their correct three-dimensional shapes, even when cells are under stress from elevated body temperatures.
Grimes said she was a little skeptical at first about pursuing studies with HSP70 because it is a commonly known protein, but she found Mohanan’s initial data intriguing. “Vishnu found that if we increased the expression level of HSP70, the NOD2 Crohn’s mutants were able to respond to bacterial cell wall fragments. A hallmark of the NOD2 mutations is inability to respond to these fragments….Basically, HSP70 keeps the protein around—it kind of watches over and protects NOD2, and keeps it from going in the cellular trash can,” Grimes explains.
The researchers tested three human cell lines in their study: kidney cells, colon cells, and white blood cells. In the next phase of the study, patient tissue will be examined to determine if NOD2 levels can be controlled via HSP70 expression. Read the study abstract.
Read more
