title: Interplay between parkin and p53 governs a physiological homeostasis that is disrupted in Parkinson's disease and cerebral cancer.
abstract: Parkin is responsible for most autosomal juvenile recessive cases of Parkinson's disease (PD). Besides its well-characterized function as ubiquitin ligase, we previously established that parkin could repress p53 at the transcriptional level. Interestingly, p53 was recently shown to upregulate parkin, suggesting a feedback loop by which parkin and p53 interplay, thereby contributing to their physiological homeostasis. This equilibrium is disrupted in both PD and cerebral cancer. Thus, when parkin is mutated in PD, its transcriptional ability to repress p53 is abolished. Therefore, p53 elevation could likely contribute to the exacerbated cell death observed in PD-affected brains. Inversely, in brain-associated tumors linked to p53 mutations, the transcriptional control of parkin is reduced, and thereby, parkin expression is lowered. The reduction in parkin level could, in turn, contribute to an increase in the levels of transcriptionally inactive p53 that could explain, at least in part, the defect in cellular apoptotic commitment observed in cerebral cancer. Here, we discuss in detail the various studies demonstrating the importance of the functional interplay between parkin and p53 and its impairment by pathogenic mutations likely contributing to the etiology of PD and gliomas.
authors.affiliation: Institut de Pharmacologie Moléculaire et Cellulaire, Team Fondation pour la Recherche Médicale and Labex Distalz, Valbonne, France.
authors.forename: F
authors.initials: F
authors.lastname: Checler
authors.forename: C
authors.initials: C
authors.lastname: Alves da Costa
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005786:Gene Expression Regulation; D006706:Homeostasis / Q000502:physiology; D006801:Humans; 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*
chemical_list: D016159:Tumor Suppressor Protein p53; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein