JUN 27, 2016 3:09 PM PDT

TSRI Scientists Find New Cancer Drug Target in Dual-Function Protein

Scientists at The Scripps Research Institute (TSRI) have identified a protein that launches cancer growth and appears to contribute to higher mortality in breast cancer patients.

The new findings, published June 27, 2016 in the journal Nature Structural & Molecular Biology, suggest that future therapies might target this protein, called GlyRS, to halt cancer growth.

“We have potentially found an important target for anti-cancer treatment,” said TSRI Professor Xiang-Lei Yang, who led the study.
The Scripps Research Institute Professor Xiang-Lei Yang (left) and Research Associate Zhongying Mo were key authors of the new study. (TSRI)
Catching a Double Agent

Since the early days of life on Earth, GlyRS has played a role in protein synthesis, helping cells function and grow.

The new study, a collaboration with Professor Patrick Griffin’s lab on the Florida campus of TSRI, reveals that GlyRS is actually a double agent—in addition to its biologically essential role in making proteins, it can help to further modify proteins in a way that launches cancer growth.

The researchers found that overexpression of GlyRS may lead to too little p27—a protein than Yang compared to a stop sign for cell growth.

Specifically, the team found that GlyRS creates a protective shield around a modifier protein, called NEDD8, and safely “chaperones” it to meet its target protein, called cullin. With NEDD8 in place, cullin is activated to degrade p27.

Kept at the right levels, p27 regulates the cell cycle, stopping potential cancer growth. But when GlyRS levels increase, too much p27 gets degraded and cells multiply unchecked. 

“Cancer cells hijack and over-exaggerate the system,” said TSRI Research Associate Zhongying Mo, first author of the study. “This can lead to tumorigenesis.”

This process is especially dangerous given GlyRS’s additional function in protein synthesis, which supplies cancers with the proteins they need to keep growing. “Ultimately, both functions are linked to cell proliferation and tumorigenesis,” Yang said.

Indeed, when Mo analyzed data from a breast cancer tissue database, she found that patients with increased GlyRS had higher mortality.

Although this research is at the basic stage, the team believes it could guide future cancer diagnostics and therapies. For example, measuring GlyRS may provide a marker to help doctors predict how quickly a patient’s cancer might progress.

The team now plans to study the effects of GlyRS in different types of cancer and the possibility of developing a drug to inhibit GlyRS.

In addition to Yang, Griffin and Mo, authors of the study “Neddylation requires glycyl-tRNA synthetase to protect activated E2,” were Qian Zhang, Ze Liu, Yi Shi and Litao Sun of TSRI’s California campus and Janelle Lauer of TSRI’s Florida campus.

This research was supported by the National Institutes of Health (grant R01GM088278).
_________
FOR MORE INFORMATION
Xiang-Lei Yang Biosketch
Yang Lab Website
Nature Structural & Molecular Biology
About the Author
  • The Scripps Research Institute (TSRI) is one of the world's largest independent, not-for-profit organizations focusing on research in the biomedical sciences. TSRI is internationally recognized for its contributions to science and health, including its role in laying the foundation for new treatments for cancer, rheumatoid arthritis, hemophilia, and other diseases. An institution that evolved from the Scripps Metabolic Clinic founded by philanthropist Ellen Browning Scripps in 1924, the institute now employs about 2,700 people on its campuses in La Jolla, CA, and Jupiter, FL, where its renowned scientists-including two Nobel laureates-work toward their next discoveries. The institute's graduate program, which awards PhD degrees in biology and chemistry, ranks among the top ten of its kind in the nation. For more information, see www.scripps.edu.
You May Also Like
APR 29, 2021
Cell & Molecular Biology
Cancer Cell Fate Influenced by Dietary Amino Acid
APR 29, 2021
Cancer Cell Fate Influenced by Dietary Amino Acid
This work could one day open up dietary therapeutic options for cancer.
MAY 05, 2021
Immunology
Novel 3D Bio-printed Leukemia Model Shows Potential for Treatment Testing Platform
MAY 05, 2021
Novel 3D Bio-printed Leukemia Model Shows Potential for Treatment Testing Platform
Three-dimensional (3D) printing has become a common technique over the past two decades. Now, the technique has been ado ...
MAY 31, 2021
Immunology
Engineering Faster, More Agile T Cell Cancer Fighters
MAY 31, 2021
Engineering Faster, More Agile T Cell Cancer Fighters
Cell therapies use engineered T cells extracted from the patient’s own immune system to rally an attack on tumors. ...
JUN 11, 2021
Cell & Molecular Biology
Bad Fat in the Tumor Microenvironment May Disrupt Killer T Cells
JUN 11, 2021
Bad Fat in the Tumor Microenvironment May Disrupt Killer T Cells
The immune system can detect and destroy pathogenic and cancerous cells, but sometimes those dangerous cells can evade t ...
JUN 21, 2021
Cancer
Analyzing breast implant topography and associated immune responses
JUN 21, 2021
Analyzing breast implant topography and associated immune responses
In an effort to understand how breast implants influence the immune system, researchers from MIT have led an analysis to ...
JUL 16, 2021
Drug Discovery & Development
Machine Learning Ranks Cancer Drugs by Efficacy
JUL 16, 2021
Machine Learning Ranks Cancer Drugs by Efficacy
A machine learning algorithm developed by researchers at the Queen Mary University of London in the UK can rank cancer d ...
Loading Comments...