Ring finger and FYVE-like domain-containing E3 ubiquitin protein ligase (RFFL)

Ring finger and FYVE-like domain-containing E3 ubiquitin protein ligase (RFFL) is a membrane-associated E3 ubiquitin ligase of the RING finger class, responsible for promoting the ubiquitin-mediated degradation of various substrate proteins via the proteasome[3][5]. It plays key regulatory roles in multiple biological processes, notably apoptosis (through ubiquitination of caspases 8 and 10), cell migration (via mTORC2/PRR5L), regulation of the tumor suppressor p53/TP53, endosomal trafficking, and membrane protein recycling[2][3][4]. RFFL also targets misfolded cystic fibrosis transmembrane conductance regulator (CFTR) for degradation, contributing to cystic fibrosis pathology[2][4]. Aberrant function or expression of RFFL is directly implicated in diseases such as cancer (through oncogenic suppression of apoptosis and p53 pathway), cardiac arrhythmias (notably Long QT syndrome), and cystic fibrosis[3][4]. RFFL is considered a relevant drug target in oncology and other diseases associated with ubiquitin-proteasome system dysregulation[1][2]. At present, RFFL-targeting drugs are not approved, but modulation of E3 ligase activity remains an area of active research for novel therapeutics[1].

Other names

E3 ubiquitin-protein ligase rififylinRNF189RNF34LCARP-2FringRififylinCaspase regulator CARP2Caspases-8 and -10-associated RING finger protein 2FYVE-RING finger protein SakuraRING finger and FYVE-like domain-containing protein 1RING finger protein 189RING finger protein 34-likeRING-type E3 ubiquitin transferase rififylinCaspase 8 and 10 associated RING protein-2CARP2FRINGRIFIFYLIN

Promotion of substrate ubiquitination leading to proteasomal degradation; Inhibition of apoptosis via degradation of caspases 8 and 10; Negative regulation of TP53 tumor suppressor via ubiquitination; Regulation of CFTR surface expression (relevant to cystic fibrosis)