E3 ubiquitin-protein ligase RNF31 (RNF31)

E3 ubiquitin-protein ligase RNF31 (RNF31/HOIP) is an atypical RBR (Ring-between-Ring) family member that acts as the catalytic core of the linear ubiquitin chain assembly complex (LUBAC)[1][3]. It specifically mediates the formation of Met1-linked (linear) polyubiquitin chains, which are crucial for strong NF-κB activation downstream of inflammatory stimuli such as interleukin-1, TNF-α, and Toll-like receptor agonists[1][3]. RNF31 also regulates transcriptional repression of steroidogenic genes by cooperating with DAX-1 and is involved in stabilizing proteins such as estrogen receptor α (ERα) and p53, impacting cell proliferation and apoptosis[2][4]. Dysregulation or overexpression of RNF31 is associated with aggressive cancer phenotypes (breast and liver), poor prognosis, and particular immunodeficiencies and autoinflammatory syndromes[1][3]. The protein contains multiple functional domains (RING, IBR, PUB, and UBA) relevant to substrate interaction and ligase activity, and is being studied as a cancer therapeutic and prognostic biomarker[1][4][3][6]. No approved drugs directly target RNF31, but it is recognized as a potential intervention point for modulating inflammation and tumor progression.

Other names

HOIPZIBRAFLJ10111FLJ23501PaulHOIL-1-interacting proteinIMD115Zinc in-between-RING-finger ubiquitin-associated domain proteinRING finger protein 31RING-type E3 ubiquitin transferase RNF31

Inhibition of linear ubiquitin chain assembly; Modulation of NF-κB signaling; Disruption of substrate ubiquitination (e.g., estrogen receptor α and p53)