Loss of function Cbl-c mutations in solid tumors.

Receptor Tyrosine Kinase (RTK) signaling is essential for normal biological processes and disruption of this regulation can lead to tumor initiation and progression. Cbl proteins (Cbl, Cbl-b and Cbl-c) are a family of RING finger (RF) ubiquitin ligases that negatively regulate a variety of RTKs, including EGFR, MET, and RET. Recent studies have identified Cbl mutations associated with human myeloid neoplasias in approximately 5% of the cases.

Mutant p53 cooperates with ETS2 to promote etoposide resistance.

Mutant p53 (mtp53) promotes chemotherapy resistance through multiple mechanisms, including disabling proapoptotic proteins and regulating gene expression. Comparison of genome wide analysis of mtp53 binding revealed that the ETS-binding site motif (EBS) is prevalent within predicted mtp53-binding sites. We demonstrate that mtp53 regulates gene expression through EBS in promoters and that ETS2 mediates the interaction with this motif.