Our new manuscript on the ubiquitin ligase HOIL-1L is out in iScience!

Our work on “The ubiquitin ligase HOIL-1L regulates immune responses by interacting with linear ubiquitin chains” is now online (iScience). Carlos, the last PhD student of the Ikeda Lab at IMBA (Austria) did a great job here.

“The ubiquitin ligase HOIL-1L regulates immune responses by interacting with linear ubiquitin chains”
Carlos Gomez-Diaz, Gustav Jonsson, Katrin Schodl, Luiza Deszcz, Annika Bestehorn, Kevin Eislmayr, Jorge Almagro, Anoop Kavirayani, Mayu Seida, Lilian M Fennell, Astrid Hagelkruys, Pavel Kovarik, Josef M Penninger, Fumiyo Ikeda


Our study on LUBAC generating heterotypic ubiquitin chains is publihsed in eLife.

The Ikeda lab (MIB, Japan and IMBA, Austria) and the Haselbach lab (IMP,  Austria) published a paper entitled “The linear ubiquitin chain assembly complex LUBAC generates heterotypic ubiquitin chains” in eLife.

In this study, we found that LUBAC generates heterotypic ubiquitin chains (oxyester bond-based branching on the linear ubiquitin chains) dependently on the catalytic site in the HOIL-1L RING2 domain. We also revealed the first 3D structural model of an E3 ligase complex called LUBAC.

This was a work of Alan of his PhD study. Congratulations to everyone who was involved!

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Our study on HOIP ubiquitination is out in the EMBO Journal!

“The ubiquitin code written on the ubiquitin ligase HOIP regulates inflammation”

A small modifier protein ubiquitin regulates every aspect of biology. Our new study revealed a mechanism how inflammation is regulated by ubiquitination. The mechanism involves ubiquitin modification of the ubiquitin ligase HOIP, a known immune signaling regulator.

HOIP generates a special type of the ubiquitin code namely a linear (Met1-linked) ubiquitin chain and regulates inflammatory signaling cascades induced by various cytokines. An open question was how the ligase HOIP is regulated in upon cytokine stimuli in cells.

In this study, we tacked this question by focusing on the posttranslatioal modification of HOIP. We found that one ubiquitination site in HOIP is important in the regulation of TNF-induced apoptosis and NF-kB activation. By using a newly generated knockin mice in which the HOIP ubiquitination site is mutated, we found that HOIP ubiquitination at the site plays collaborative role with SHARPIN, one of the two partner proteins of HOIP.

In summary, we found that the modulation of HOIP by ubiquitination is one of the mechanisms how its downstream signaling cascade is regulated.

Title: Site-specific ubiquitination of the E3 ligase HOIP regulates apoptosis and immune signaling

Authors: Lilian M. Fennell, Carlos Gomez Diaz, Luiza Deszcz, Anoop Kavirayani, David Hoffmann, Kota Yanagitani, Alexander Schleiffer, Karl Mechtler, Astrid Hagelkruys, Josef Penninger, Fumiyo Ikeda

EMBO Journal
DOI: 10.15252/embj.2019103303

A link to the press release page (in Japanese):