Parkin: much more than a simple ubiquitin ligase.
Parkin is mainly a cytosolic protein involved in a subset of Parkinson's disease (PD) cases referred to as autosomal juvenile recessive forms of PD. Most studies have established as a dogma that parkin function could be resumed as an ubiquitin ligase activity. Accordingly, several cellular functions ascribed to parkin derive from its ability to ubiquitinate a series of proteins, thereby rendering them prone to proteasomal degradation. Several lines of data indicated that parkin could display antiapoptotic properties and we demonstrated that indeed, parkin could downregulate the p53-dependent pathway. However, we showed that such function remained independent of parkin's ability to act as an ubiquitin ligase. Thus, we established that parkin repressed p53 transcription by physically interacting with its promoter. Here, we describe this novel parkin-associated transcription factor function and we speculate on putative additional transcriptional targets.
Institut de Pharmacologie Moléculaire et Cellulaire et Institut de NeuroMédecine Moléculaire, Equipe Labellisée Fondation pour la Recherche Médicale, Sophia-Antipolis, Valbonne, France.
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Alves da Costa
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Checler
D000818:Animals; D001921:Brain / Q000378:metabolism; D016923:Cell Death / Q000235:genetics; D006801:Humans; D051379:Mice; D009154:Mutation / Q000235:genetics; D010300:Parkinson Disease / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*
D016159:Tumor Suppressor Protein p53; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein