RANBP2-type and C3HC4-type zinc finger-containing protein 1 (RBCK1)

RANBP2-type and C3HC4-type zinc finger-containing protein 1 (RBCK1), also known as HOIL-1, is an E3 ubiquitin-protein ligase and an essential component of the Linear Ubiquitin Chain Assembly Complex (LUBAC) (UniProt, 2024). LUBAC is unique in its ability to catalyze the formation of head-to-tail linear ubiquitin chains, which play a critical role in the activation of the canonical NF-kappa-B pathway and the regulation of programmed cell death (Kirisako et al., 2006). RBCK1 acts as a scaffold and regulatory subunit within this complex, ensuring the stability and specificity of linear ubiquitination on substrates like NEMO and RIPK1 (Gerlach et al., 2011). Mutations in the RBCK1 gene are associated with severe clinical phenotypes, including Polyglucosan body myopathy 1, which involves glycogen accumulation in muscles and the heart, and a combined immunodeficiency with autoinflammation (Boisson et al., 2012). In the context of oncology, RBCK1 is frequently upregulated in various malignancies, where it promotes tumor cell survival and chemoresistance by enhancing pro-survival signaling (NCBI, 2024). Consequently, RBCK1 and the LUBAC complex are being investigated as potential therapeutic targets for the development of novel anti-inflammatory and anti-cancer agents.

Other names

RBCK1HOIL-1HOIL1RNF54XIBPPUD-1HBV-associated factor 4HAF4UBCE7IP3

Inhibition of linear ubiquitin chain assembly complex (LUBAC) activity and subsequent NF-kappa-B signaling pathway suppression.