Ubiquitin ligase SMURF2 enhances epidermal growth factor receptor stability and tyrosine-kinase inhibitor resistance
Paramita Ray, Krishnan Raghunathan, Aarif Ahsan, Uday Sankar Allam, Shirish Shukla, Venkatesha Basrur, Sarah L. Veatch, Theodore S. Lawrence, Mukesh K. Nyati, Dipankar Ray
Abstract
knockdown decreased EGFR steady-state levels and sensitized lung cancer cells. Overall, we propose that SMURF2-mediated polyubiquitination of L858R/T790M EGFR competes with acetylation-mediated receptor internalization that correlates with enhanced receptor stability; therefore, disruption of the E3-E2 complex may be an attractive target to overcome TKI resistance.
Topics & Concepts
T790MEpidermal growth factor receptorErlotinibUbiquitin ligaseCancer researchTyrosine kinaseUbiquitinBiologyEGFR inhibitorsChemistryCell biologySignal transductionMolecular biologyReceptorBiochemistryGefitinibGeneUbiquitin and proteasome pathwaysLung Cancer Treatments and MutationsProtein Degradation and Inhibitors