• Andrew Webb

Releasing the brakes on immune responses by inhibition of HOIL-1L.

Tumour Necrosis Factor (TNF) plays a central role in our body’s immune system, helping to control inflammation that occurs as our body responds to damage or infection. Cells often respond dramatically to TNF, sensed as a danger signal through a cascade of signal transduction from receptor engagement at the cell surface. The outcome of this signal is highly diverse, and strongly dependent on the regulation of the key signalling events such as phosphorylation and ubiquitination.

For many years, scientists around the world have been studying how TNF sends signals to the immune system, yet the levers that regulate this process are still being discovered. Here Fuseya et al, use Aurora IonOpticks columns to identify the regulatory sites of ubiquitin modification that act as the key molecular switches of TNF signalling member HOIL-1L. This work identified this protein's importance in the clearance of intracellular Salmonella infection and highlights it as a promising target, particularly in immunocompromised hosts.

The HOIL-1L ligase modulates immune signalling and cell death via monoubiquitination of LUBAC. Nature Cell Biology. 2020 May 11: Vol. 22, pp663–673


Fuseya Y, Fujita H, Kim M, Ohtake F, Nishide A, Sasaki K, Saeki Y, Tanaka K, Takahashi R, Iwai K