Post-Translational Regulation Using Degrons in Ewing Sarcoma.

The EWSR1::FLI1 (EF1) chimeric transcription factor is pathognomonic in Ewing Sarcoma (EwS) and is often the sole oncogenic mutation harbored by EwS tumors. Disrupting the function of EF1 to study its role in tumor biology using small molecules has proven challenging. Here, we describe complementary strategies to incorporate inducible protein degrons into the endogenous EWSR1::FLI1 locus in patient-derived EwS cells. These systems enable precise control over the timing and level of EF1 protein abundance as well as downstream functional analyses.