Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Discovering the secrets of the enigmatic caspase-6


Researchers identified the mechanisms underlying the innate immune function of the enzyme caspase-6, offering ways to combat viral infection, inflammatory diseases and cancer.

St. Jude Children's Research Hospital scientists have identified previously unknown functions of the enigmatic enzyme caspase-6. The findings show that caspase-6 is a key regulator of innate immunity, inflammasome activation and host defense.

Senior author Thirumala-Devi Kanneganti, Ph.D., and first author Min Zheng, Ph.D., both of the Department of Immunology, discovered a key component in cell death processes that allow for possible, new ways to fight viruses.

Credit: St. Jude Children's Research Hospital

Modulation of caspase-6 could be beneficial for treating viral diseases like influenza and other inflammatory diseases including cancer. The work appears as an advance online publication today in Cell.

Caspases are a family of enzymes that regulate programmed cell death (how a cell self-destructs), inflammation and other biological functions. Caspase-6 has previously been characterized as an executioner caspase in a non-inflammatory form of cell death called apoptosis. Caspase-6 has also been linked to neurological disorders like Alzheimer's disease and Huntington disease.

However, the full range of the enzyme's function was not well understood. Now, researchers have discovered for the first time how caspase-6 regulates the ZBP1-NLRP3 inflammasome.

"We contributed to the fundamental understanding of caspase-6, which has remained a mystery in the field for decades," said senior author Thirumala-Devi Kanneganti, Ph.D., of the St. Jude Department of Immunology. "Caspase-6 has essential functions in innate immunity, inflammation and in driving PANoptosis."

Cell death and innate immune function

The Kanneganti laboratory previously was first to identify ZNA-binding protein 1 (ZBP1) as an innate immune sensor of influenza, an RNA virus. Their work also revealed that ZBP1 triggers inflammatory cell death in the form of pyroptosis, apoptosis and necroptosis, which together are known as PANoptosis.

PANoptosis is an inflammatory death pathway regulated by components of a structure termed the PANoptosome, which mediates cell death that cannot be assigned to any of the single cell death pathways described previously. In this study, the scientists found that caspase-6 played a critical role in this process.

The researchers found that caspase-6 interacts with RIPK3 to facilitate the recruitment of RIPK3 to the ZBP1-PANoptosome. This makes caspase-6 crucial for assembly of this ZBP1-mediated inflammatory cell death-inducing complex. In line with these findings, the researchers demonstrated that caspase-6 is required for ZBP1-mediated PANoptosis during viral infection.

"Caspase-6 deficiency in mice leads to increased susceptibility to influenza virus infection and higher levels of viral replication in the lungs," said first author Min Zheng, Ph.D., of the St. Jude Department of Immunology. "It is likely that the caspase-6-mediated inflammatory cell death pathway is essential to fighting other viruses that activate similar innate immune pathways, potentially including other respiratory viruses."

The discovery that caspase-6 is a key component in cell death processes has diverse implications for human health, suggesting that modulation of caspase-6 could be a beneficial approach to infectious and inflammatory disease treatment.

The other authors are Rajendra Karki and Peter Vogel, both of St. Jude.

The research at St. Jude was funded in part by grants from the National Institutes of Health (AI101935, AI124346, AR056296 and CA163507) and ALSAC, the fundraising and awareness organization of St. Jude.


St. Jude Children's Research Hospital

St. Jude Children's Research Hospital is leading the way the world understands, treats and cures childhood cancer and other life-threatening diseases. It is the only National Cancer Institute-designated Comprehensive Cancer Center devoted solely to children. Treatments developed at St. Jude have helped push the overall childhood cancer survival rate from 20 percent to 80 percent since the hospital opened more than 50 years ago. St. Jude freely shares the breakthroughs it makes, and every child saved at St. Jude means doctors and scientists worldwide can use that knowledge to save thousands more children. Families never receive a bill from St. Jude for treatment, travel, housing and food -- because all a family should worry about is helping their child live. To learn more, visit or follow St. Jude on social media at @stjuderesearch.

Media Contact

Katy Hobgood


Katy Hobgood | EurekAlert!
Further information:

Further reports about: CANCER Cell Immunology RIPK3 apoptosis cell death childhood cancer inflammatory viruses

More articles from Life Sciences:

nachricht A new view of microscopic interactions
01.07.2020 | University of Missouri-Columbia

nachricht Microscope allows gentle, continuous imaging of light-sensitive corals
01.07.2020 | Marine Biological Laboratory

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: ILA Goes Digital – Automation & Production Technology for Adaptable Aircraft Production

Live event – July 1, 2020 - 11:00 to 11:45 (CET)
"Automation in Aerospace Industry @ Fraunhofer IFAM"

The Fraunhofer Institute for Manufacturing Technology and Advanced Materials IFAM l Stade is presenting its forward-looking R&D portfolio for the first time at...

Im Focus: AI monitoring of laser welding processes - X-ray vision and eavesdropping ensure quality

With an X-ray experiment at the European Synchrotron ESRF in Grenoble (France), Empa researchers were able to demonstrate how well their real-time acoustic monitoring of laser weld seams works. With almost 90 percent reliability, they detected the formation of unwanted pores that impair the quality of weld seams. Thanks to a special evaluation method based on artificial intelligence (AI), the detection process is completed in just 70 milliseconds.

Laser welding is a process suitable for joining metals and thermoplastics. It has become particularly well established in highly automated production, for...

Im Focus: A structural light switch for magnetism

A research team from the Max Planck Institute for the Structure of Dynamics (MPSD) and the University of Oxford has managed to drive a prototypical antiferromagnet into a new magnetic state using terahertz frequency light. Their groundbreaking method produced an effect orders of magnitude larger than previously achieved, and on ultrafast time scales. The team’s work has just been published in Nature Physics.

Magnetic materials have been a mainstay in computing technology due to their ability to permanently store information in their magnetic state. Current...

Im Focus: Virtually Captured

Biomechanical analyses and computer simulations reveal the Venus flytrap snapping mechanisms

The Venus flytrap (Dionaea muscipula) takes only 100 milliseconds to trap its prey. Once their leaves, which have been transformed into snap traps, have...

Im Focus: NASA observes large Saharan dust plume over Atlantic ocean

NASA-NOAA's Suomi NPP satellite observed a huge Saharan dust plume streaming over the North Atlantic Ocean, beginning on June 13. Satellite data showed the dust had spread over 2,000 miles.

At NASA's Goddard Space Flight Center in Greenbelt, Maryland, Colin Seftor, an atmospheric scientist, created an animation of the dust and aerosols from the...

All Focus news of the innovation-report >>>



Industry & Economy
Event News

Dresden Nexus Conference 2020: Same Time, Virtual Format, Registration Opened

19.05.2020 | Event News

Aachen Machine Tool Colloquium AWK'21 will take place on June 10 and 11, 2021

07.04.2020 | Event News

International Coral Reef Symposium in Bremen Postponed by a Year

06.04.2020 | Event News

Latest News

First exposed planetary core discovered

01.07.2020 | Physics and Astronomy

Energy-saving servers: Data storage 2.0

01.07.2020 | Power and Electrical Engineering

Laser takes pictures of electrons in crystals

01.07.2020 | Physics and Astronomy

Science & Research
Overview of more VideoLinks >>>