Odilia Sianto Rose Hills
Interplay Between Protein Stability and Catalytic Activity in Kinases
Kinases are dynamic enzymes that carry out signal transduction in the cell. Many kinases rely on chaperones to protect them from unfolding and poise them for signaling. Chaperoning of kinases by HSP90/CDC37 has been shown to be critical for cancer cell growth and survival, and blocking this interaction could represent a new avenue of treatment for cancers. However, the biophysical nature of kinase chaperoning is not well understood. For my project, I plan to study the kinase BRAF, which, when mutated, is an important driver of oncogenesis and makes the kinase dependent on HSP90/CDC37 to protect it from degradation. In human cells, I will examine how other activating mutations affect BRAF chaperoning to understand how HSP90/CDC37 regulates client kinases. This work could reveal how mutations alter kinase structure to promote interaction with chaperones and inform the development of strategies to block this interaction therapeutically.