A5073311972- RNA Research and Splicing
- Genomics and Chromatin Dynamics
- RNA modifications and cancer
- Ubiquitin and proteasome pathways
- Neurological diseases and metabolism
- Prion Diseases and Protein Misfolding
- Prostate Cancer Treatment and Research
- Protein Degradation and Inhibitors
- Nuclear Receptors and Signaling
- RNA and protein synthesis mechanisms
- Cancer-related gene regulation
Max Planck Institute for Molecular Genetics
2020-2023
McGill University
2018
Abstract Thousands of genetic variants in protein-coding genes have been linked to disease. However, the functional impact most is unknown as they occur within intrinsically disordered protein regions that poorly defined functions 1–3 . Intrinsically can mediate phase separation and formation biomolecular condensates, such nucleolus 4,5 This suggests mutations proteins may alter condensate properties function 6–8 Here we show a subset disease-associated separation, cause mispartitioning into...
Transcription factors are among the most attractive therapeutic targets but considered largely 'undruggable' in part due to intrinsically disordered nature of their activation domains. Here we show that aromatic character domain androgen receptor, a target for castration-resistant prostate cancer, is key its activity as transcription factor, allowing it translocate nucleus and partition into transcriptional condensates upon by androgens. On basis our understanding interactions stabilizing...
A central step in the pathogenesis of prion diseases is conformational transition cellular protein (PrPC) into scrapie isoform, denoted PrPSc Studies transgenic mice have indicated that this conversion requires a direct interaction between PrPC and PrPSc; however, insights underlying mechanisms are still missing. Interestingly, only subfraction converted scrapie-infected cells, suggesting not all species suitable substrates for conversion. On basis observation can form homodimers under...
Summary Transcription factors are among the most attractive therapeutic targets but considered largely undruggable due to intrinsically disordered nature of their activation domains. Here we show that aromatic character domain androgen receptor, a target for castration resistant prostate cancer, is key its activity as transcription factor by allowing it partition into transcriptional condensates. Based on this knowledge optimized structure small molecule inhibitor, previously identified...