Nav: Home

STAT2: Much more than an antiviral protein

October 25, 2016

A protein known for guarding against viral infections leads a double life, new research shows, and can interfere with cell growth and the defense against parasites. In a new paper publishing 25 October in the open-access journal PLOS Biology, Johnathan Ho and Uwe Vinkemeier at the University of Nottingham, UK, and colleagues describe the duplicitous nature of this essential protein, called STAT2, which they discovered while investigating the mechanisms behind interferon signaling.

Interferons are powerful antimicrobials that can also stop the proliferation of normal and cancer cells. Since their discovery in the early 1950s, 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. This paradigm has been consistently validated and refined over the last decades. While STAT1 has since been assigned multiple additional roles, STAT2 was thought to function primarily as the partner of STAT1 in interferon signaling. The work published in PLOS Biology 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 behavior between two proteins so classically associated with co-operation," says 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 behaviors. 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 key to overcoming such limitations.
-end-
In your coverage please use this URL to provide access to the freely available article in PLOS Biology: http://dx.doi.org/10.1371/journal.pbio.2000117

Citation: Ho J, Pelzel C, Begitt A, Mee M, Elsheikha HM, Scott DJ, et al. (2016) STAT2 Is a Pervasive Cytokine Regulator due to Its Inhibition of STAT1 in Multiple Signaling Pathways. PLoS Biol 14(10): e2000117. doi:10.1371/journal.pbio.2000117

Funding: Medical Research Council http://www.mrc.ac.uk/ (grant number MR/001276/1). Received by UV. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Science and Technology Funding Council (UK) http://www.stfc.ac.uk/ (grant number ). Received by DJS (Senior Molecular Biology and Neutron Fellow). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing Interests: The authors have declared that no competing interests exist.

PLOS

Related Protein Articles:

Hi-res view of protein complex shows how it breaks up protein tangles
A new, high-resolution view of the structure of Hsp104 (heat shock protein 104), a natural yeast protein nanomachine with six subunits, may show news ways to dismantle harmful protein clumps in disease.
Breaking the protein-DNA bond
A new Northwestern University study finds that unbound proteins in a cell break up protein-DNA bonds as they compete for the single-binding site.
FASEB Science Research Conference: Protein Kinases and Protein Phosphorylation
This conference focuses on the biology of protein kinases and phosphorylation signaling.
Largest resource of human protein-protein interactions can help interpret genomic data
An international research team has developed the largest database of protein-to-protein interaction networks, a resource that can illuminate how numerous disease-associated genes contribute to disease development and progression.
STAT2: Much more than an antiviral protein
A protein known for guarding against viral infections leads a double life, new research shows, and can interfere with cell growth and the defense against parasites.
More Protein News and Protein Current Events

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Anthropomorphic
Do animals grieve? Do they have language or consciousness? For a long time, scientists resisted the urge to look for human qualities in animals. This hour, TED speakers explore how that is changing. Guests include biological anthropologist Barbara King, dolphin researcher Denise Herzing, primatologist Frans de Waal, and ecologist Carl Safina.
Now Playing: Science for the People

#534 Bacteria are Coming for Your OJ
What makes breakfast, breakfast? Well, according to every movie and TV show we've ever seen, a big glass of orange juice is basically required. But our morning grapefruit might be in danger. Why? Citrus greening, a bacteria carried by a bug, has infected 90% of the citrus groves in Florida. It's coming for your OJ. We'll talk with University of Maryland plant virologist Anne Simon about ways to stop the citrus killer, and with science writer and journalist Maryn McKenna about why throwing antibiotics at the problem is probably not the solution. Related links: A Review of the Citrus Greening...