The Interplay Among PINK1/PARKIN/Dj-1 Network During Mitochondrial Quality Control in Cancer Biology: Protein Interaction Analysis
Keywords: oxidative stress, pink1, parkin, dj-1, cancer biology, mitochondrial quality control, protein-protein interactions.
Abstract
PARKIN (E3 ubiquitin ligase PARK2), PINK1 (PTEN induced kinase 1) and DJ-1 (PARK7) are proteins involved in autosomal recessive parkinsonism, and carcinogenic processes. In damaged mitochondria, PINK1's importing into the inner mitochondrial membrane is prevented, PARKIN presents a partial mitochondrial localization at the outer mitochondrial membrane and DJ-1 relocates to mitochondria when oxidative stress increases. Depletion of these proteins result in abnormal mitochondrial morphology. PINK1, PARKIN, and DJ-1 participate in mitochondrial remodeling and actively regulate mitochondrial quality control. In this review, we highlight that PARKIN, PINK1, and DJ-1 should be regarded as having an important role in Cancer Biology. The STRING database and Gene Ontology (GO) enrichment analysis were performed to consolidate knowledge of well-known protein interactions for PINK1, PARKIN, and DJ-1 and envisage new ones. The enrichment analysis of KEGG pathways showed that the PINK1/PARKIN/DJ-1 network resulted in Parkinson disease as the main feature, while the protein DJ-1 showed enrichment in prostate cancer and p53 signaling pathway. Some predicted transcription factors regulating PINK1, PARK2 (PARKIN) and PARK7 (DJ-1) gene expression are related to cell cycle control. We can therefore suggest that the interplay among PINK1/PARKIN/DJ-1 network during mitochondrial quality control in cancer biology may occur at the transcriptional level. Further analysis, like a systems biology approach, will be helpful in the understanding of PINK1/PARKIN/DJ-1 network.
Más información
Título de la Revista: | CELLS |
Volumen: | 7 |
Número: | 10 |
Editorial: | MDPI |
Fecha de publicación: | 2018 |
Página de inicio: | 154 |
Idioma: | Inglés |
Financiamiento/Sponsor: | FONDECYT grant number 11130192 |
URL: | https://www.mdpi.com/2073-4409/7/10/154 |
DOI: |
DOI: 10.3390/cells7100154 |
Notas: | ISI |