Parkin acts as a transcription factor modulating presenilin-1 and presenilin-2 promoter transactivations

Excerpt

Parkin is associated to autosomal recessive early-onset Parkinson's disease. Parkin acts as an E3-ubiquitin ligase involved in the proteasome-mediated degradation of various substrates. It has been suggested that pathogenic mutations of parkin, abolishing its ubiquitin-ligase activity, could explain the accumulation of proteins and lead to neuronal death by apoptosis. However, besides this function, additional parkin-dependent cellular pathways exist. We demonstrated that parkin is a direct transcriptional repressor of the tumor suppressor p53 [1]. p53 regulates the expression and functions of presenilin-1 (PS1) and presenilin-2 (PS2), two members of the gamma secretase complex involved in the production of the amyloid β peptide (Aβ) and parkin could control the homeostasis of intracellular Aβ. These findings prompted us to investigate whether parkin could control presenilins and if so, whether it is via a direct transcriptional control of PS promoters or indirectly, via p53. …