title: Ring finger protein 146/Iduna is a poly(ADP-ribose) polymer binding and PARsylation dependent E3 ubiquitin ligase.
abstract: Recent findings suggest that Ring finger protein 146 (RNF146), also called iduna, have neuroprotective property due to its inhibition of Parthanatos via binding with Poly(ADP-ribose) (PAR). The Parthanatos is a PAR dependent cell death that has been implicated in many human diseases. RNF146/Iduna acts as a PARsylation-directed E3 ubquitin ligase to mediate tankyrase-dependent degradation of axin, thereby positively regulates Wnt signaling. RNF146/Iduna can also facilitate DNA repair and protect against cell death induced by DNA damaging agents or γ-irradiation. It can translocate to the nucleus after cellular injury and promote the ubiquitination and degradation of various nuclear proteins involved in DNA damage repair. The PARsylation-directed ubquitination mediated by RNF146/Iduna is analogous to the phosphorylation-directed ubquitination catalyzed by Skp1-Cul1-F-box (SCF) E3 ubiquitin complex. RNF146/Iduna has been found to be implicated in neurodegenerative disease and cancer development. Therefore modulation of the PAR-binding and PARsylation dependent E3 ligase activity of RNF146/Iduna could have therapeutic significance for diseases, in which PAR and PAR-binding proteins play key pathophysiologic roles.
authors.affiliation: National Neuroscience Institute, Singapore.
authors.forename: Zhi-dong
authors.initials: ZD
authors.lastname: Zhou
authors.forename: Christine Hui-shan
authors.initials: CH
authors.lastname: Chan
authors.forename: Zhi-cheng
authors.initials: ZC
authors.lastname: Xiao
authors.forename: Eng-king
authors.initials: EK
authors.lastname: Tan
mesh_terms: D000595:Amino Acid Sequence; D016923:Cell Death; D002471:Cell Transformation, Neoplastic; D019610:Cytoprotection; D004260:DNA Repair; D006801:Humans; D008969:Molecular Sequence Data; D019636:Neurodegenerative Diseases / Q000378:metabolism; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism*; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D011506:Proteins / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D060449:Wnt Signaling Pathway
chemical_list: D011506:Proteins; C024857:poly(ADP)-ribosylated proteins; D011064:Poly Adenosine Diphosphate Ribose; C561932:RNF146 protein, human; D044767:Ubiquitin-Protein Ligases