New research has uncovered how a complex protein pivotal in the development of cancer, viral infection and autoimmune diseases is activated. The discovery answers a key question about one of the most widely-researched proteins in human biology, which has been the subject of tens of thousands of research papers and millions of pounds in research funding.
Jiazhen Zhang, a research student in Professor Sir Philip Cohen's laboratory at the University of Dundee, uncovered how the protein complex, called NF-κB, is activated. The results are published today in the Biochemical Journal.
NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) is a protein complex that controls transcription of DNA. NF-κB is found in almost all animal cell types and plays a key role in regulating the immune response to infection. Incorrect regulation of NF-κB has been linked to cancer, inflammatory, and autoimmune diseases, septic shock, viral infection, and improper immune development.
"NF-κB has been the subject of a vast amount of research for many years as it plays a critical role in inflammatory diseases and cancer," said Sir Philip. "It has been known for some time that the protein is activated by a kinase called IKKβ but there has been split opinion with regards to how the kinase itself is switched on.
"We have confirmed that another kinase, TAK1, is involved, but surprisingly it isn't sufficient to switch on IKKβ. Two other events need to happen in addition, namely the formation of an unusual type of ubiquitin chain and its attachment to IKKβ and then the addition of a second phosphate group on to IKKβ which remarkably is carried out by IKKβ itself. It is only then that IKKβ becomes competent to switch on NF-κB.
"This is complex biochemistry but working out the details of how proteins are switched on and off is how new ways to develop improved drugs to treat disease are identified. For example, the enzyme that makes the ubiquitin chains needed to activate IKKβ could now be targeted to develop a drug to treat inflammatory diseases."
The research was carried out in the Medical Research Council Protein Phosphorylation and Ubiquitylation Unit (MRC-PPU) at Dundee.
Peter Shepherd, Chair of the Biochemical Journal Editorial Board, said, "This signalling pathway is critical for a wide range of cellular responses, particularly stress responses. Understanding how this pathway is regulated is hugely important, and this paper finally clarifies one of the key steps in this process. This is important in not only understanding the disease process, but in the quest to develop new therapies that target this signalling pathway."
Alastair Stewart | Eurek Alert!
More than just a mechanical barrier – epithelial cells actively combat the flu virus
04.05.2016 | Helmholtz-Zentrum für Infektionsforschung
Discovery of a fundamental limit to the evolution of the genetic code
03.05.2016 | Institute for Research in Biomedicine (IRB Barcelona)
Using an ultra fast-scanning atomic force microscope, a team of researchers from the University of Basel has filmed “living” nuclear pore complexes at work for the first time. Nuclear pores are molecular machines that control the traffic entering or exiting the cell nucleus. In their article published in Nature Nanotechnology, the researchers explain how the passage of unwanted molecules is prevented by rapidly moving molecular “tentacles” inside the pore.
Using high-speed AFM, Roderick Lim, Argovia Professor at the Biozentrum and the Swiss Nanoscience Institute of the University of Basel, has not only directly...
If a person pushes a broken-down car alone, there is a certain effect. If another person helps, the result is the sum of their efforts. If two micro-particles are pushing another microparticle, however, the resulting effect may not necessarily be the sum their efforts. A recent study published in Nature Communications, measured this odd effect that scientists call “many body.”
In the microscopic world, where the modern miniaturized machines at the new frontiers of technology operate, as long as we are in the presence of two...
Researchers from the Max Planck Institute Stuttgart have developed self-propelled tiny ‘microbots’ that can remove lead or organic pollution from contaminated water.
Working with colleagues in Barcelona and Singapore, Samuel Sánchez’s group used graphene oxide to make their microscale motors, which are able to adsorb lead...
Neutron scattering and computational modeling have revealed unique and unexpected behavior of water molecules under extreme confinement that is unmatched by any known gas, liquid or solid states.
In a paper published in Physical Review Letters, researchers at the Department of Energy's Oak Ridge National Laboratory describe a new tunneling state of...
Honeycomb structures as the basic building block for industrial applications presented using holo pyramid
Researchers of the Alfred Wegener Institute (AWI) will introduce their latest developments in the field of bionic lightweight design at Hannover Messe from 25...
27.04.2016 | Event News
15.04.2016 | Event News
12.04.2016 | Event News
04.05.2016 | Physics and Astronomy
04.05.2016 | Physics and Astronomy
04.05.2016 | Materials Sciences