Summary
This research project aims to understand how the ubiquitin-proteasome system regulates the retinoblastoma (Rb) tumor suppressor protein, its impact on cell cycle progression, and its role in mediating response to Cdk4/6 inhibitors in cancer.
Regulation of the retinoblastoma (Rb) tumor suppressor by the ubiquitin-proteasome system
US · IL
NIH
grant
awarded
#nih-5F31CA288070-02
What they want
The project will investigate the regulation of the Rb protein by the ubiquitin-proteasome system. This includes identifying the specific ubiquitin ligase (E3) responsible for Rb degradation and determining the timing of this degradation within the cell cycle using mass-spectrometry and CRISPR/Cas9. Furthermore, the research will explore how Rb degradation influences cell cycle progression and sensitivity to Cdk4/6 inhibitors through various biochemical, genetic, and fluorescent imaging approaches, including the engineering of cell lines with inducible non-degradable Rb mutants.
Deliverables
- Identification of the ubiquitin ligase (E3) that degrades Rb
- Determination of the timing of Rb degradation in the cell cycle
- Investigation of how the degradation of Rb affects cell cycle progression
- Determination of the extent to which disrupting Rb degradation affects sensitivity to Cdk4/6 inhibition
- Engineered cell lines expressing an inducible form of a non-degradable Rb mutant
Technical requirements
- Mass-spectrometry
- CRISPR/Cas9 approach
- Live-cell imaging
- Biochemical approaches
- Genetic approaches
- Fluorescent imaging approaches
