Researchers at UC Berkeley published a study Wednesday detailing a potential new target for cancer drugs lying behind a “secret compartment” of a common protein complex.
In order to locate the target, researchers probed the origins of proteins that stimulate cellular growth and found that many come from a surprising location — a usually blocked section of the protein complex eIF3. According to Jamie Cate, a campus professor of molecular and cell biology who led the study, new treatments for cancer could focus on closing the door to reduce the growth of cancerous cells.
Certain protein molecules can play a role in the development of cancer, said Amy Lee, an assistant professor at Brandeis University who co-authored the study during her time as a UC Berkeley postdoctoral scholar.
“Proteins are the workers in the cell,” Lee said. “If you have too many (proteins) made, that can lead to overactive cell growth.”
Cate compared eIF3 to an “antique desk” with a secret compartment used to store important documents. This secret compartment, he said, is normally blocked by amino acids.
To promote cell growth, a specific type of mRNA molecule, which carries the genetic blueprint for the production of specific proteins, binds to eIF3. This process causes eIF3’s door to open, beginning to turn the mRNAs into proteins.
According to Cate, the mRNAs that bind to this area of eIF3 are “heavily implicated” in cancer.
Because the proteins produced through this pathway appear to control only cell growth and proliferation rather than other cellular functions, they could be a specific target for cancer drugs. A certain protein produced from the c-Jun gene, for example, is known to be correlated with cancer, according to Cate.
“If we could inhibit the making of this c-Jun protein, we might be able to stop cancer or even kill the cancer cells,” Cate said.
Two different labs will continue to work on research connected to the protein target. Lee, who has started a new lab at Brandeis University, will focus on learning more about how eIF3 regulates translation in order to potentially develop small molecules to block it.
“If you could find small molecular compounds that could block the activity they discovered, that might be a way to prevent cancer cells from growing,” said campus molecular and cell biology professor Donald Rio.
Cate’s lab at UC Berkeley will continue to use cryoelectron microscopy to see the part of the mRNA that unlocks the “secret compartment” on the eIF3 protein, which, Cate said, will enable the researchers to work with the protein more accurately.
The research was funded by the National Institute of General Medical Sciences, through the Center for RNA Systems Biology at UC Berkeley.
Contact Mira Chaplin at [email protected].