Ring finger protein 31 (RNF31) (RNF31)

Ring finger protein 31 (RNF31), also known as HOIP, is the essential catalytic subunit of the Linear Ubiquitin Chain Assembly Complex (LUBAC), which is the only known E3 ligase complex capable of generating M1-linked linear ubiquitin chains [1, 9]. These chains play a pivotal role in the canonical NF-kappaB signaling pathway and the regulation of cell death by stabilizing signaling complexes downstream of receptors like TNFR1 [1, 5]. In various malignancies, including B-cell lymphomas and breast cancer, RNF31 is often overexpressed or mutated, leading to hyperactivation of NF-kappaB and resistance to apoptosis [2, 7]. Consequently, RNF31 has emerged as a promising therapeutic target, with small-molecule inhibitors such as HOIPIN-8 and stapled peptides being developed to sensitize tumor cells to immune-mediated killing and chemotherapy [5, 7]. However, because germline deficiency in RNF31 is associated with severe immunodeficiency and autoinflammation in humans, therapeutic modulation of this target requires careful management of potential systemic safety risks [6, 10].

Other names

HOIPHOIL-1-interacting proteinZIBRAZinc In-Between-RING-Finger Ubiquitin-Associated Domain ProteinPaul

Inhibition of the catalytic activity of RNF31 to prevent the assembly of M1-linked linear ubiquitin chains, thereby suppressing NF-kappaB activation and sensitizing cells to TNF-mediated apoptosis [1, 5, 7].