Forkhead Box O3a requires BAF57, a subunit of chromatin remodeler SWI/SNF complex for induction of p53 up ‐regulated modulator of apoptosis (Puma) in a model of Parkinson’s disease

Parkinson's disease results from the death of dopaminergic neurons in the substantia nigra pars compacta region of the brain. The mechanism of neuron death still remains elusive. Here, we investigated the regulation of a pro ‐apoptotic protein, PUMA by transcription factor, FoxO3a in a model of PD. In healthy cells, transcription factor FoxO3a is localized in cytosol as an inactive complex bound with 14‐3‐3 protein. 6‐OHDA, a Parkinson's disease mimetic, treatment leads to a number of post‐translational modifi cations of FoxO3a which in turn causes its nuclear translocation. In nucleus, FoxO3a in association with BAF57 (a crucial member of chromatin remodeler SWI/SNF complex) binds with the FoxO‐binding site on Puma promoter. This binding results in increased PUMA expression and neuronal cell death. Thi s findings suggest that FoxO3a requires chromatin remodeler complex protein BAF57 for transcriptional activation of its target gene PUMA and subsequent neuron death in response to 6‐OHDA. AbstractParkinson's disease (PD) results from the selective loss of dopaminergic neurons of substantia nigra pars compacta region of the midbrain. It has been reported that the transcription factor forkhead Box O3a (FoxO3a) is activated and induces pro ‐apoptotic protein such as Bcl‐2‐interacting mediator of cell death (BIM) and p53 up‐regulated modulator of apoptosis (PUMA) in variety of neuron death paradigms. Activity of FoxO3a is governed by its post‐translational ...
Source: Journal of Neurochemistry - Category: Neuroscience Authors: Tags: ORIGINAL ARTICLE Source Type: research