Critical interactions of neuronal transcription factor REST with stabilizer TRF2
|Year of publication||2022|
|MU Faculty or unit|
Glioblastoma is the most common and malignant brain tumor in adults. Glioblastoma is highly resistant to chemotherapy and radiotherapy. So far, there has been no successful treatment. Recent studies revealed a strong correlation between glioblastoma tumorigenicity and the aberrant expression of REST, the main repressor of neural stem cell differentiation .
The fate of the REST inside cells is mainly regulated by ubiquitylation. The primary protecting role is played by telomeric factor TRF2 that forms a complex with REST and protects it from ubiquitylation and therefore from proteasomal degradation . TRF2 also forms the core of the shelterin complex that shields chromosome ends against unwanted end-joining and DNA repair machinery. REST indirectly regulates TRF2 expression; thus, it affects shelterin complex formation . REST TRF2 complex disruption is a promising target of molecular therapy that will provide a dual effect on cancer stem cells.
Here, we have investigated in cell localization of REST and TRF2, and we have observed the formation of REST-TRF2 complex directly in the cell nucleus using Proximity ligation assay. We have determined the structure of transcription factor REST using cryo-electron microscopy single-particle reconstruction. A better understanding of the REST-TRF2 complex will provide valuable knowledge in development of drugs against glioblastoma.
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