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 IonOpticks Aurora Series 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.

Read the full paper
The HOIL-1L ligase modulates immune signalling and cell death via monoubiquitination of LUBAC.
Nature Cell Biology. 2020 May 11: Vol. 22, pp663–673.
doi: https://doi.org/10.1038/s41556-020-0517-9

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

Commentary by Andrew Webb, PhD.

About the author
Andrew has over 15 years’ experience in the field of chromatography and mass spectrometry. He is the lead innovator and inventor at IonOpticks, working closely with the team to test, refine and develop cutting edge techniques to support higher quality outputs and analytics from MS instruments. Andrew is also the Lab Head of the Walter and Eliza Hall Institute of Medical Research’s Proteomics Research Laboratory.