NIH Reporter #1R16GM159690-01

Mapping biophysical effects of the cellular environment on p53 and PTEN stability and aggregation

This award funds research to study how cellular environment affects the stability and aggregation of tumor suppressor proteins p53 and PTEN, aiming to inform cancer therapeutic strategies.

Description

Misfolding and aggregation to amyloid states contributes to loss-of-function phenotypes for the critical tumor suppressor proteins p53 and PTEN in cancer. Changes to cellular environments during oncogenesis may modulate the conformational landscapes of p53 and PTEN, inducing aggregation pathways or stabilizing certain conformational states, but how cellular factors interact with these central signaling proteins has not been systematically investigated. Here, we will use a comprehensive approach to measure the effect of endogenous metabolites and ubiquitination/phosphorylation posttranslational modifications on the stability and amyloid formation propensity of p53 and PTEN, enabling us to develop chemical tools to detect these states and informing new strategies for cancer therapeutics.

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