Ring finger protein 146/Iduna is a poly (ADP-ribose) polymer binding and PARsylation dependent E3 ubiquitin ligase

Zhi-Dong Zhou, Christine Hui-shan Chan, Zhi-Cheng Xiao, Eng-King Tan

    Research output: Contribution to journalArticleResearchpeer-review

    24 Citations (Scopus)

    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 I?-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.
    Original languageEnglish
    Pages (from-to)463 - 471
    Number of pages9
    JournalCell Adhesion and Migration
    Volume5
    Issue number6
    DOIs
    Publication statusPublished - 2011

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