A paradigm shift in immune response ...(pression necessary for the cell's immune...)

The question that had to be answered was how does NEMO activate NF-κB? This is where the work of the Frankfurt biochemists came in. They identified a subdomain of NEMO, called UBAN that binds selectively to a specific type of ubiquitin. This protein is ubiquitous in the cell and has various functions, acting as a multifaceted molecular signal. It can function as a single molecule (monoubiquitin) or in the form of chains (polyubiquitin).

In the scientific journal "Cell", Ivan Dikic and his colleagues report that NEMO specifically binds to linear ubiquitin chains and that this is an essential step for NF-κB activation. This came as a big surprise to the team, since it was previously thought that other types of ubiquitin signals were critical for NEMO-dependent NF-κB activation. "This results in a paradigm change", says Ivan Dikic, "it means, that current knowledge on NF-κB activation and the role of linear ubiquitin chains needs to be updated".

In cooperation with the group of Soichi Wakatsuki, NEMO's structure could be solved. The work demonstrates that the UBAN domain binds to a linear ubiquitin chain according to the key-and-lock-principle. "These new findings not only explain the atomic details of ubiquitin chain selectivity, but can also provide useful insights into developing therapy for targeting the NF-κB pathway", reports Soichi Wakatsuki. Increased activation of the NF-κB pathway is known to be linked to development of different diseases such as cancer and inflammation.

The discovery also has direct medical relevance. "We are happy that this basic scientific discovery may explain the detrimental effect of NEMO mutations in patients suffering from X-linked ectoderma
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