When the protein STING (pink) is activated, the transcription factor TFEB (green) is shuttled into the nucleus, where it stimulates the production of lysosomes. (CREDIT: Jay Xiaojun Tan).
By: Asher Jones
A protein called STING, previously shown to control a pathway that contributes to antiviral signaling, also plays an important role in cellular stress clearance and cell survival, according to a new paper published in Molecular Cell.
“It was quite surprising that STING has a protective function for cells to reduce stress and damage in addition to its well-known role in inflammation,” said senior author Jay Xiaojun Tan, assistant professor of cell biology, School of Medicine, and the University of Pittsburgh School of Medicine/UPMC Aging Institute.
“Our findings suggest that the balance of STING’s two functions is important for the health of cells and could have implications for future development of therapeutics for age-related diseases,” added first author Bo Lv, a postdoctoral researcher in Tan’s lab.
In healthy human cells, DNA is packaged inside the nucleus and mitochondria. When DNA leaks out into the fluid component of the cell known as the cytosol, it means that something is wrong.
“Cytosolic DNA is a danger signal associated with infections, cellular stress, cancer and other diseases,” explained Tan. “Cells have a warning system to detect DNA in the cytosol, which involves activation of STING, which in turn coordinates inflammation necessary to combat these threats.”
While short bursts of STING-mediated inflammation are crucial, in some people this pathway is chronically “on,” a state that has been linked with neurodegeneration and other diseases of aging, as well as normal aging.
To learn more about potential benefits of STING activation in response to diverse stresses, Tan and his team analyzed the full set of proteins within cells. They found that when STING was activated, two transcription factors called TFEB and TFE3 were shuttled to the nucleus of cells, where they activated genes that resulted in the production of more lysosomes.
“Lysosomes are organelles that are involved in autophagy, a cellular process that cleans up damaged material, almost like a housekeeping or recycling system,” said Tan. “In response to STING activation, cells used TFEB and TFE3 to produce more lysosomes and increase autophagy.”
When the protein STING (pink) is activated, the transcription factor TFEB (green) is shuttled into the nucleus, where it stimulates the production of lysosomes. (CREDIT: Jay Xiaojun Tan).