Features | Partner Sites | Information | LinkXpress
Sign In
GLOBETECH PUBLISHING LLC
GLOBETECH PUBLISHING LLC
GLOBETECH MEDIA

Tumors Benefit from Molecular Switch That Blocks T-cell Interferon Production

By BiotechDaily International staff writers
Posted on 26 Jun 2013
A molecular switch causes immune system T-cells to convert from oxidative phosphorylation (OXPHOS) to aerobic glycolysis, a change that inhibits the production of the inflammatory cytokine interferon gamma.

The move from OXPHOS to aerobic glycolysis is a hallmark of T-cell activation and was thought to be required to meet the metabolic demands of proliferation. However, why proliferating cells would adopt this less efficient way to produce energy, especially in an oxygen-rich environment, has been a mystery.

Investigators at the Washington University School of Medicine (St. Louis, MO, USA) studied the role of the known molecular switch GAPDH glyceraldehyde 3-phosphate dehydrogenase) in the conversion of T-cells from OXPHOS to aerobic glycolysis.

GAPDH is an enzyme of approximately 37 kDa that catalyzes the sixth step of glycolysis and thus serves to break down glucose for energy and carbon molecules. As its name indicates, GAPDH catalyzes the conversion of glyceraldehyde 3-phosphate to D-glycerate 1,3-bisphosphate. This conversion occurs in the cytosol of the cell in two coupled steps. The first is favorable and allows the second unfavorable step to occur. In addition to this long established metabolic function, GAPDH has recently been implicated in several nonmetabolic processes, including transcription activation, initiation of apoptosis, and ER to Golgi vesicle shuttling.

The investigators reported in the June 6, 2013, issue of the journal Cell that aerobic glycolysis was specifically required for effector function in T-cells but that this pathway was not necessary for proliferation or survival. When activated T-cells were provided with co-stimulation and growth factors but were blocked from engaging glycolysis, their ability to produce interferon gamma was markedly compromised. This defect was translational and was regulated by the binding of GAPDH to interferon gamma mRNA.

"The proteins involved in glycolysis do not just disappear when glycolysis is turned off—they are pretty stable proteins, so they can hang around in the cell and participate in other processes," said senior author Dr. Erika Pearce, assistant professor of pathology and immunology at the Washington University School of Medicine. "In T-cells this can be a problem since one of these proteins, GAPDH, can inhibit the production of interferon gamma. It is like an on-off switch, and all we need to do to flip it is change the availability of sugar. T-cells often can go everywhere—tumors, inflammation, infections—but sometimes they do not do anything. If we can confirm that this same switch is involved in these failures in the body, we might be able to find a way to put the fight back into those T-cells."

"T-cells can get into tumors, but unfortunately they are often ineffective at killing the cancer cells," said Dr. Pearce. "Lack of the ability to make interferon gamma could be one reason why they fail to kill tumors. By understanding more about how sugar metabolism affects interferon production, we may be able to develop treatments that fight tumors by enhancing T-cell function."

Related Links:
Washington University School of Medicine



Channels

Drug Discovery

view channel
Image: Molecular model of the protein Saposin C (Photo courtesy of Wikimedia Commons).

Nanovesicles Kill Human Lung Cancer Cells in Culture and in a Mouse Xenograft Model

Nanovesicles assembled from the protein Saposin C (SapC) and the phospholipid dioleoylphosphatidylserine (DOPS) were shown to be potent inhibitors of lung cancer cells in culture and in a mouse xenograft model.... Read more

Biochemistry

view channel

Possible New Target Found for Treating Brain Inflammation

Scientists have identified an enzyme that produces a class of inflammatory lipid molecules in the brain. Abnormally high levels of these molecules appear to cause a rare inherited eurodegenerative disorder, and that disorder now may be treatable if researchers can develop suitable drug candidates that suppress this enzyme.... Read more

Lab Technologies

view channel
Image: The FLUOVIEW FVMPE-RS Gantry microscope (Photo courtesy of Olympus).

New Multiphoton Laser Scanning Microscope Configurations Expand Research Potential

Two new configurations of a state-of-the-art multiphoton laser scanning microscope extend the usefulness of the instrument for examining rapidly occurring biological events and for obtaining images from... Read more

Business

view channel

Roche Acquires Signature Diagnostics to Advance Translational Research

Roche (Basel, Switzerland) will advance translational research for next generation sequencing (NGS) diagnostics by leveraging the unique expertise of Signature Diagnostics AG (Potsdam, Germany) in biobanks and development of novel NGS diagnostic assays. Signature Diagnostics is a privately held translational oncology... Read more
 
Copyright © 2000-2015 Globetech Media. All rights reserved.