Ring finger protein 31 (HOIP) (HOIP)

Ring finger protein 31 (RNF31), commonly known as HOIP, is the essential catalytic subunit of the Linear Ubiquitin Chain Assembly Complex (LUBAC). It is the only known E3 ubiquitin ligase capable of generating M1-linked (linear) ubiquitin chains, which act as critical scaffolds for the recruitment and activation of the IKK complex and subsequent NF-kappaB signaling (UniProt Q96EP0). Beyond its role in pro-survival signaling, HOIP is a key regulator of the cell death rheostat, preventing TNF-induced apoptosis and necroptosis by stabilizing the TNFR1-associated signaling complex (PubMed: 21455180). In the context of oncology, HOIP is frequently overexpressed or mutated in activated B-cell-like diffuse large B-cell lymphoma (ABC-DLBCL), where it drives constitutive NF-kappaB activation and tumor cell survival (PubMed: 21455181). Therapeutic interest in HOIP focuses on the development of small-molecule inhibitors targeting its RING-Between-RING (RBR) catalytic domain to suppress pathological inflammation and sensitize resistant cancer cells to apoptosis-inducing therapies (PubMed: 32694140).

Other names

RNF31HOIL-1-interacting proteinZIBRAZinc finger protein binding to RNALUBAC catalytic subunit

Inhibition of the RBR (RING-Between-RING) catalytic domain to prevent the assembly of M1-linked linear ubiquitin chains, thereby blocking NF-kappaB activation and sensitizing cells to TNF-induced apoptosis.