RESUMEN
Linear ubiquitination is an important post-translational modification that has been discovered in recent years. The linear ubiquitin chain is formed by the linkage of glycine residue of one ubiquitin protein to the methionine residue of another ubiquitin. This process is regulated by the linear ubiquitin chain assembly complex (LUBAC) and the OTU deubiquitinase with linear linkage specificity (OTULIN). Linear ubiquitination is involved in various biological processes, including immune response, inflammation, and cell apoptosis. Recent studies have shown that linear ubiquitination is closely related to the occurrence, development, and drug resistance of tumors by affecting signaling pathways such as NF-κB and Wnt/β-catenin. The research progress on the function of LUBAC and OTULIN in tumors was reviewed in this paper.
RESUMEN
Linear ubiquitination plays an important role in tumor and the immune system. Linear ubiq- uitin chain assembly complex ( LUBAC) is the only known ubiquitin ligase that can catalyze the synthesis of linear ubiquitin chains. We found that ubiquitin ligase ariadne homolog 2 ( ARIH2) was a new interacting protein of LUBAC, and ARIH2 inhibited the level of linear ubiquitination of substrates by LUBAC. We further demonstrated that ARIH2 interacted with HOIP by Co-IP experiment, and that HOIP interacted with ARIH2 through the ZF-NZF ( zinc finger-Npl4-Zinc finger) domain by GST pull-down experiments. Moreover, we showed that LUBAC could not modify ARIH2 by linear ubiquitination; On the contrary, ARIH2 inhibited the linear ubiquitination level of LUBAC substrates. The mechanism may be that ARIH2 affects the ubiquitination level of SHANK-associated RH domain interacting protein ( SHARP- IN ), thereby affecting the enzyme activity of LUBAC, which leads to the weakening of the linear ubiquit- ination level of LUBAC to the substrate.