Protein modifications pointing to cancer

August 28, 2018

Cells use different signals to react to stress and to inform other body cells. Triggers are, for example, cancer or inflammatory diseases. A central signaling pathway of stress response is the modification of proteins called ADP-ribosylation. Small molecules (ADP ribose) are added to precisely defined protein sites to control protein function.

Determine all protein modifications of a sample at once

Researchers at the Department of Molecular Mechanisms of Disease at the University of Zurich (UZH) have recently developed a method with which they can, for the first time, use tissue samples to investigate all proteins outside the cells that carry ADP-ribosylation as modification. With the identification of this ADP-ribosylome, the exact positions at which the proteins were modified can also be determined. These data allow conclusions to be drawn about activated signaling pathways in the cells.

Specifically, the scientists investigated cells in the muscle tissue of mice. The enzyme ARTC1, which exclusively modifies proteins that are located outside the cells, is almost only found in this type of tissue. It was surprising that even in the absence of stress many of the extracellular muscle proteins already showed the modification. In the interior of the cell, however, ADP-ribosylation is only triggered in stress situations. "This suggests that ADP-ribosylation is involved in many signaling pathways in an as yet unknown way and has several ways of controlling cell function," says Mario Leutert, first author of the paper.

Identifying diseases by modified proteins

The scientists suspect that these protein modifications are also involved in disease processes. Substances that block ADP-ribosylation act against certain forms of breast and ovarian cancer and can reduce inflammation. Since the changes in all proteins in a tissue sample can now be investigated at once, the modifications at selected protein positions can be investigated in healthy and sick individuals. Modified ADP-ribosylation patterns indicate a disease and allow conclusions to be drawn about therapeutic strategies.

New diagnostic and therapeutic possibilities

Michael Hottiger's group has also developed the first antibody that recognizes a mono-ADP-ribosylated protein. "Initial results in collaboration with the University Hospital Zurich (USZ) show that such antibodies could be used to predict the course of certain types of cancer," says Hottiger. The researchers are currently developing additional antibodies against selected ADP-ribosylation sites that were discovered in the new study.

They also want to investigate whether such antibodies also have therapeutic potential - for example, against cancer. "We still have a lot to learn about ADP-ribosylation. But we are convinced that the medical benefits for cancer, infections and neurodegenerative diseases might be enormous," concludes Hottiger.
-end-


University of Zurich

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.