A protein known for guarding against viral infections leads a double life, and can interfere with cell growth and the defence against parasites, finds new research from The University of Nottingham.
In a new paper publishing on 25 October in the open-access journal PLOS Biology, Johnathan Ho, Uwe Vinkemeier and colleagues at the University describe the duplicitous nature of this essential protein, called STAT2, which they discovered while investigating the mechanisms behind interferon signalling.
Interferons are powerful antimicrobials that can also stop the proliferation of normal and cancer cells.
Intense research into the modus operandi of these molecules culminated 25 years ago, when it was found that interferon requires STAT2 and a closely related partner protein, STAT1, to function.
In the intervening years further studies discovered that STAT1 has multiple additional roles, but STAT2 was still thought to function primarily as the partner of STAT1 in interferon signalling.
The work published in PLOS Biology, however, reveals an entirely novel aspect of STAT2 as an inhibitor of STAT1, extending its reach far beyond interferon and antiviral immunity.
“It’s astounding to see such robust antagonistic behaviour between two proteins so classically associated with co-operation,” says post-graduate student Johnathan Ho, the paper’s first author.
This new research uncovers the molecular mechanism of STAT2’s two-faced nature, alongside the development of novel tools that can disarm its enabling and inhibitory behaviours.
These new tools make it possible to study previously inaccessible features of STAT2 functioning such as regulation of cellular growth and ageing, blood poisoning and infectious diseases.
Moreover, although interferon therapies have proven indispensable for treating a wide range of ailments like viral hepatitis, multiple sclerosis and cancers, their application is hindered by serious adverse effects and unpredictable therapeutic outcomes.
The insights offered by this work will be a key to overcoming such limitations.