UD team develops new method for producing proteins critical to medical research

March 31, 2010

Scientists at the University of Delaware have developed a new method for producing proteins critical to research on cancer, Alzheimer's, and other diseases.

Developed by Zhihao Zhuang, UD assistant professor of chemistry and biochemistry, and his research group, the chemical method yields hundredsfold more ubiquitylated proteins than current approaches. Such proteins may hold the key to revealing such mysteries as how cancer cells gain resistance to cancer drugs.

The advance is reported in the April issue of Nature Chemical Biology, the leading journal in the field of chemical biology. Zhuang's co-authors include graduate students Junjun Chen and Jialiang Wang and postdoctoral fellow Yongxing Ai, all from UD, and Lajos Haracska, a researcher in the Institute of Genetics at the Hungarian Academy of Sciences.

Ubiquitin is a small protein, the basis of Nobel Prize-winning research in 2004, which deemed the molecule the "kiss of death" for its role in tagging damaged or unneeded proteins for the cell's waste disposal in the constant process of protein generation and degradation. In recent years, the non-proteolytic functions of ubiquitin in diverse cellular processes, including protein trafficking, immune response, and DNA damage tolerance, have been discovered at a rapid pace, and it has become clear that ubiquitin plays far-broader roles in cell biology.

However, preparing sufficient samples of ubiquitylated proteins for study has been a major challenge facing scientists.

The availability of these proteins is critical for Zhuang and members of his research team, who are working at the interface of chemistry and biology trying to understand the molecular basis of human cancer development and prevention.

The new method for developing ubiquitylated proteins, which Zhuang and his team developed, combines the power of intein chemistry and disulfide crosslinking to bond ubiquitin to another essential protein called proliferating cell nuclear antigen.

"Our yield is hundredsfold higher compared to the commonly used enzymatic approach," Zhuang says. "We also have the flexibility of modifying the selected residues, which has not been possible with the previous approach."

In investigating the effect of the differently modified proteins, Zhuang and his group also revealed a surprising phenomenon regarding ubiquitylation.

"We found that ubiquitin as a protein modifier is far more flexible than we have thought. This property distinguishes ubiquitylation from other better studied protein post-translational modifications, such as phosphorylation and acetylation," Zhuang says.

The new UD approach will help researchers studying ubiquitin biology by providing the means to prepare milligrams of protein samples for in-depth structural and functional characterization.

SInce the publication of the work online in Nature Chemical Biology, Zhuang has received requests for samples from research groups across the United States.

Additionally, the new approach has already opened up doors to new research in Zhuang's own laboratory, where he and his team are investigating new anti-cancer therapies.
-end-
The research on the new method was supported by Zhuang's laboratory start-up funding from UD, as well as a recent grant from the University of Delaware Research Foundation (UDRF).

University of Delaware

Related Cancer Articles from Brightsurf:

New blood cancer treatment works by selectively interfering with cancer cell signalling
University of Alberta scientists have identified the mechanism of action behind a new type of precision cancer drug for blood cancers that is set for human trials, according to research published in Nature Communications.

UCI researchers uncover cancer cell vulnerabilities; may lead to better cancer therapies
A new University of California, Irvine-led study reveals a protein responsible for genetic changes resulting in a variety of cancers, may also be the key to more effective, targeted cancer therapy.

Breast cancer treatment costs highest among young women with metastic cancer
In a fight for their lives, young women, age 18-44, spend double the amount of older women to survive metastatic breast cancer, according to a large statewide study by the University of North Carolina at Chapel Hill.

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.

Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.

Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.

Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.

More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.

New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.

American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.

Read More: Cancer News and Cancer Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.