Library Dissertation Showcase

Investigating dj-1 interaction with p53 in relation to Parkinson’s disease

  • Year of Publication:
  • 2022

Parkinson’s disease is caused by loss of dopaminergic neurones in the brain. The neuroprotective protein DJ-1 is thought to stop the activation of apoptosis by the tumour suppressant protein p53 to stop the development of Parkinson’s disease. p53 can initiate apoptosis in response to oxidative stress by upregulating transcription of BAX. To investigate if DJ-1 can inhibit p53 activation of BAX an electromobility shift assay was employed to see the binding of p53 to synthetic, fluorescently labelled promotor sequences. Promotors for the proteins BAX, p21, GPx1 and PCNA were studied to observe shifting by p53 and how their electromobility changed with the inclusion of DJ-1. Furthermore, the assay was carried out with reduced and oxidised DJ-1 to investigate how the oxidation state affects the interaction. The study found that wild type DJ-1 partially inhibited p53 tetramers from binding to all four promotor sequences when under reducing conditions, but lost activity on the BAX and p21 promotor when oxidised. The findings show DJ-1 can inhibit p53 transcriptional activity with promotor specificity, and that changes in the oxidation of DJ-1 can change its ability to act on p53. The results support findings that DJ-1 inhibits p53 transcriptional activity on BAX and p21 to stop the promotion of apoptosis in dopaminergic neurons to protect from Parkinson’s disease development. However, the lack of oxidised DJ-1 activity on p53 binding to the BAX promotor goes against some published findings, which is suspected to be due to variance in the oxidation state of DJ-1 used.

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