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Citation
Popovic, R., Celardo, I., Yu, Y., Costa, A.C., Loh, S.H.Y., Martins, L.M. (2021). Combined Transcriptomic and Proteomic Analysis of Perk Toxicity Pathways.  Int. J. Mol. Sci. 22(9): 4598.
FlyBase ID
FBrf0248801
Publication Type
Research paper
Abstract

In Drosophila, endoplasmic reticulum (ER) stress activates the protein kinase R-like endoplasmic reticulum kinase (dPerk). dPerk can also be activated by defective mitochondria in fly models of Parkinson's disease caused by mutations in pink1 or parkin. The Perk branch of the unfolded protein response (UPR) has emerged as a major toxic process in neurodegenerative disorders causing a chronic reduction in vital proteins and neuronal death. In this study, we combined microarray analysis and quantitative proteomics analysis in adult flies overexpressing dPerk to investigate the relationship between the transcriptional and translational response to dPerk activation. We identified tribbles and Heat shock protein 22 as two novel Drosophila activating transcription factor 4 (dAtf4) regulated transcripts. Using a combined bioinformatics tool kit, we demonstrated that the activation of dPerk leads to translational repression of mitochondrial proteins associated with glutathione and nucleotide metabolism, calcium signalling and iron-sulphur cluster biosynthesis. Further efforts to enhance these translationally repressed dPerk targets might offer protection against Perk toxicity.

PubMed ID
PubMed Central ID
PMC8124185 (PMC) (EuropePMC)
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Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Int. J. Mol. Sci.
    Title
    International journal of molecular sciences
    ISBN/ISSN
    1422-0067
    Data From Reference
    Alleles (4)
    Genes (12)
    Natural transposons (1)
    Experimental Tools (2)
    Transgenic Constructs (4)