The new findings have the potential to improve our understanding of cancers and a multitude of other diseases.
Researchers at La Jolla Institute for Immunology (LJI) have finally discovered the role of an enzyme named O-GlcNAc transferase (OGT) in maintaining cell health. The findings, which were published in the Proceedings of the National Academies of Sciences, offer crucial insights into cellular biology and could pave the way for significant medical breakthroughs.
“Many diseases are related to OGT function,” says LJI Instructor Xiang Li, Ph.D., who served as the first author for the new study. “For example, many studies have shown abnormal OGT function in cancer, diabetes, and cardiovascular disease.”
The new study, spearheaded by Li and co-led by LJI Professor Anjana Rao, Ph.D., and LJI Assistant Professor Samuel Myers, Ph.D., is the first to show that OGT controls cell survival by regulating a critical protein called mTOR.
“OGT is important for every cell in the body,” explains Myers. “Thanks to this research, we now have a model we can use for future studies into what each part of OGT does.”
The one and only OGT
OGT is an enzyme called a transferase. This type of enzyme carries out a job called glycosylation, where sugar molecules are added to recently synthesized proteins. OGT is unique among transferases because it modifies proteins within cells, rather than proteins on the cell surface or secreted proteins.
In fact, OGT’s job of glycosylation is so important that embryonic cells will die without it. But until now, scientists were in the dark as to why.
As Myers explains, the essential nature of OGT is what makes it so hard to study. Scientists usually study enzymes and other proteins by developing cells that lack the genes for those proteins. They generate the new, dysfunctional cells and then investigate how things have gone wrong.
But with OGT, that kind of experiment would be over before it even began. Because there is only one OGT, scientists haven’t been able to delete it or reduce its function without simply killing the very cells they need to study. “We knew OGT was essential for cell survival, but for more than 20 years we didn’t know why,” says Li.
For the new study, Li was able to get around that problem by using an inducible system to delete the OGT gene. He worked with mouse embryonic stem cells and then used an inducible version of a protein known as Cre to delete the gene for OGT. This meant that the cells could grow normally until the scientists decided to activate the process, after which cells that had lost the OGT gene began to stop proliferating and die.
The team found that deleting the gene for OGT led to an abnormal increase in the function of a key enzyme called mTOR that regulates cell metabolism. Deleting the gene for OGT also fueled an essential but potentially dangerous process in cells called mitochondrial oxidative phosphorylation.
Why is mitochondrial oxidative phosphorylation so dangerous? This process in cells is part of a delicate pathway that allows cells to produce ATP (the molecule that powers a cell). ATP can be produced by glycolysis as well as by mitochondrial oxidative phosphorylation, and disturbing this balance can have devastating consequences for cells.
Fortunately, OGT safeguards mTOR activity and mitochondrial fitness by keeping protein synthesis running smoothly and regulating amino acid levels within cells. Importantly, the researchers discovered the same protective role for OGT in CD8+ T cells, which suggests the enzyme works the same way across mammalian cell types, not just in mouse embryonic stem cells.
Researchers to the rescue
Even the dysfunctional cells lacking OGT weren’t doomed forever. The scientists were able to “rescue” the dysfunctional cells using a new cutting-edge technology for gene editing called CRISPR/Cas9.
By asking whether a second gene in the mouse embryonic stem cells would restore the growth of cells lacking OGT, Li found that mTOR and mitochondrial oxidative phosphorylation were hyperactivated in cells lacking OGT, and the cells could be rescued by damping down their function.
This is good news for scientists hoping to learn more about OGT’s role in the body. “Now that we can delete the gene for OGT while keeping cells alive, we can try restoring just pieces of OGT to learn more about how OGT works to keep cells alive,” says Myers.
Li says his new discovery may allow researchers to further study the role of OGT and potentially find therapeutic targets to counteract abnormal activity. “In the future, we hope our research could help shed light on issues related to dysfunctional OGT in cancer and other diseases,” Li says.
![](https://www.nanoappsmedical.com/wp-content/uploads/2017/05/spacer.jpg)
News
The Silent Battle Within: How Your Organs Choose Between Mom and Dad’s Genes
Research reveals that selective expression of maternal or paternal X chromosomes varies by organ, driven by cellular competition. A new study published today (July 26) in Nature Genetics by the Lymphoid Development Group at the MRC [...]
Study identifies genes increasing risk of severe COVID-19
Whether or not a person becomes seriously ill with COVID-19 depends, among other things, on genetic factors. With this in mind, researchers from the University Hospital Bonn (UKB) and the University of Bonn, in [...]
Small regions of the brain can take micro-naps while the rest of the brain is awake and vice versa
Sleep and wake: They're totally distinct states of being that define the boundaries of our daily lives. For years, scientists have measured the difference between these instinctual brain processes by observing brain waves, with [...]
Redefining Consciousness: Small Regions of the Brain Can Take Micro-Naps While the Rest of the Brain Is Awake
The study broadly reveals how fast brain waves, previously overlooked, establish fundamental patterns of sleep and wakefulness. Scientists have developed a new method to analyze sleep and wake states by detecting ultra-fast neuronal activity [...]
AI Reveals Health Secrets Through Facial Temperature Mapping
Researchers have found that different facial temperatures correlate with chronic illnesses like diabetes and high blood pressure, and these can be detected using AI with thermal cameras. They highlight the potential of this technology [...]
Breakthrough in aging research: Blocking IL-11 extends lifespan and improves health in mice
In a recent study published in the journal Nature, a team of researchers used murine models and various pharmacological and genetic approaches to examine whether pro-inflammatory signaling involving interleukin (IL)-11, which activates signaling molecules such [...]
Promise for a universal influenza vaccine: Scientists validate theory using 1918 flu virus
New research led by Oregon Health & Science University reveals a promising approach to developing a universal influenza vaccine—a so-called "one and done" vaccine that confers lifetime immunity against an evolving virus. The study, [...]
New Projects Aim To Pioneer the Future of Neuroscience
One study will investigate the alterations in brain activity at the cellular level caused by psilocybin, the psychoactive substance found in “magic mushrooms.” How do neurons respond to the effects of magic mushrooms? What [...]
Decoding the Decline: Scientific Insights Into Long COVID’s Retreat
Research indicates a significant reduction in long COVID risk, largely due to vaccination and the virus’s evolution. The study analyzes data from over 441,000 veterans, showing lower rates of long COVID among vaccinated individuals compared [...]
Silicon Transformed: A Breakthrough in Laser Nanofabrication
A new method enables precise nanofabrication inside silicon using spatial light modulation and laser pulses, creating advanced nanostructures for potential use in electronics and photonics. Silicon, the cornerstone of modern electronics, photovoltaics, and photonics, [...]
Caught in the actinium: New research could help design better cancer treatments
The element actinium was first discovered at the turn of the 20th century, but even now, nearly 125 years later, researchers still don't have a good grasp on the metal's chemistry. That's because actinium [...]
Innovative Light-Controlled Drugs Could Revolutionize Neuropathic Pain Treatment
A team of researchers from the Institute for Bioengineering of Catalonia (IBEC) has developed light-activated derivatives of the anti-epileptic drug carbamazepine to treat neuropathic pain. Light can be harnessed to target drugs to specific [...]
Green Gold: Turning E-Waste Into a Treasure Trove of Rare Earth Metals
Scientists are developing a process inspired by nature that efficiently recovers europium from old fluorescent lamps. The approach could lead to the long-awaited recycling of rare earth metals. A small molecule that naturally serves [...]
Cambridge Study: AI Chatbots Have an “Empathy Gap,” and It Could Be Dangerous
A new study suggests a framework for “Child Safe AI” in response to recent incidents showing that many children perceive chatbots as quasi-human and reliable. A study has indicated that AI chatbots often exhibit [...]
Nanoparticle-based delivery system could offer treatment for diabetics with rare insulin allergy
Up to 3% of people with diabetes have an allergic reaction to insulin. A team at Forschungszentrum Jülich has now studied a method that could be used to deliver the active substance into the [...]
Nanorobot kills cancer cells in mice with hidden weapon
Researchers at Karolinska Institutet in Sweden have developed nanorobots that kill cancer cells in mice. The robot's weapon is hidden in a nanostructure and is exposed only in the tumor microenvironment, sparing healthy cells. [...]