Posttranslational Modifications as Versatile Regulators of Parkin Function

E.      Rubio de la Torre; P.      Gomez-Suaga; M.      Martínez-Salvador; S.      Hilfiker

Abstract

Parkin functions as an E3 ubiquitin ligase that monoubiquitylates and polyubiquitylates proteins to regulate a variety of cellular processes. It appears that parkin functions as a multipurpose neuroprotectant in a number of toxic paradigms, and loss of parkins E3 ligase activity seems to play a pathogenic role in both inherited and sporadic Parkinsons disease (PD). Increasing evidence indicates that posttranslational modifications play a major role in regulating parkins catalytic activity, solubility, substrate selection or subcellular localization. As some of these modification events are subject to pharmacological interventions, these findings may allow for new approaches in preventing or delaying PD onset and/or progression. Here, we review how posttranslational modifications can regulate this unique multifaceted ubiquitin ligase which plays a crucial role for the survival of dopaminergic neurons.

Keywords: Dopamine, parkin, phosphorylation, S-nitrosylation, ubiquitylation, neurodegeneration, Parkinsonapos;s disease, signaling, substrate, protein interaction, localization