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A new research has revealed how a complex protein that plays a significant role in the development of cancer, viral infection and autoimmune disease, is activated. The findings of the study answer a key question about one of the most widely-researched proteins in human biology. 

NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) is a protein complex that controls transcription of DNA. It is also found in almost all animal cell types and plays a significant role in regulating the immune response to infection. Previously studies have linked incorrect regulation of NF-kB to cancer, inflammatory and autoimmune diseases. 

"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," Professor Sir Philip Cohen, at the University of Dundee, said in the press release. "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."

Findings of the study has been published in the Biochemical Journal.