ARIH2 Inhibits the Linear Ubiquitination Ligase Activity of LUBAC / 中国生物化学与分子生物学报

ABSTRACT

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.