New Understanding of Protein May Aid Fight Against Cancer
Researchers say the findings may offer insight into certain birth defects, as well.
Inside the body’s cells, the job of taking out the trash is done with the help of proteins like “MID1” that mark other proteins and cellular machinery for disposal. Now researchers think MID1’s duties include marking a protein that may be implicated in many cancers—the first time a regulator of this protein has been identified.
The findings may offer new insights into fighting cancer as well as some birth defects, says the study’s lead researcher Michael Massiah, an associate professor of chemistry.
The protein, called alpha4, is found in high concentrations in many cancers, the authors write, including liver cancer, breast cancer and adenocarcinoma, or cancer originating in fluid-releasing cells, like those in the breast, pancreas and lungs. Alpha4 also is involved in regulating the maturation of immune cells.
The study was featured on the cover of the July 19 edition of the Journal of Biological Chemistry.
“Nobody knew how [alpha4] is regulated and how it works,” says Dr. Massiah, who is among the researchers slated to occupy the new Science and Engineering Hall. “We showed that MID1 actually targets alpha4 for degradation, and we did that both in the lab and in cells. So that’s kind of exciting.”
Proteins are the workhorses that drive most of the essential functions in cells throughout the body, even the regulation of other proteins, which is critical to maintaining stability inside cells. MID1 belongs to a family of proteins that helps achieve that, tagging other proteins for disposal. Scientists already were aware, for example, that the MID1 protein helps regulate the integrity of the tube-like proteins that make up the cell architecture.
To test the lab findings that MID1 controls the protein alpha4, the researchers compared two cell lines: one created with non-functioning MID1, and another in which it operated normally. In the cells with malfunctioning MID1, the team found a threefold increase in alpha4 compared to the normally functioning cells.
Further tests, including the use of fluorescent dyes to show physical interaction between alpha4 and MID1, confirmed the findings.
The results also may lead researchers to a better understanding of a disorder called Opitz syndrome, which can be caused by genetic mutations that alter the MID1 protein. The disorder affects features along the body’s vertical midline. Symptoms include wide-spaced eyes, throat issues and, in boys, a misplacement of the urethral opening of the penis. Opitz syndrome also sometimes causes cleft lip, cleft palate and mild intellectual disability, among other problems.
In unpublished data spurred by the latest paper, Dr. Massiah says the team mimicked the MID1 mutations seen in Opitz syndrome and found they affected the ability to regulate alpha4 proteins. That led to a buildup of alpha4, suggesting that alpha4 may have a strong role in causing these birth defects, he says.
“The knowledge now that alpha4 might be part of that equation might change the game,” Dr. Massiah says. Further research, he says, may lead to drugs designed to adjust the concentration of alpha4 proteins when MID1 is not functioning normally.
Read more about this study and view renderings and video of the hall.
A hub of discovery and learning at GW.
State-of-the-art flexible learning and research space.
Eight-story building with two levels of below-ground program space.
Underground parking and ground floor retail space.
Approved by the GW Board of Trustees in October 2010.
Construction will take place between 2011 and 2014.
Estimated cost is $275 million, to be funded primarily with lease payments from Square 54 (across from GW Hospital), indirect cost reimbursement from grants and contracts supporting faculty research, and philanthropic gifts from the GW community.
To download renderings, click on thumbnail. In pop-up window, right click on large image and choose "save as" or "save image as."
Science and Engineering Hall Fact Sheet