ABSTRACT: In this project we investigated the effect of YAP1 mutations on the interactome. We investigate the effect of S61A, S109A, S127A, S138A, S143A, S367A, 5SA.
Project description:In this project we investigated the effect of YAP1 mutations on the interactome. We investigate the effect of S61A, S109A, S127A, S138A, S143A, S367A, 5SA, delta WW1, delta WW2, delta WW1/WW2
Project description:Determination of the interaction partners of endogenous UBASH3B in A549 cells (PRM) and validation of the interactome after purification of Strep C- and N-terminally tagged UBASH3B in HEK293 FlpIn cell line (DDA).
Project description:SM311 is a covalent LIMK1 inhibitor. To verify the specificity of SM311 towards LIMK1, a chemoproteomic competition experiment was set up with a biotin adduct of SM311, namely SM429. This adduct was immobilised on Streptactin beads and used to enrich proteins binding to SM429. Preincubation with an excess of SM311 was used as control to outcompete and block the binding of SM429. In the competition setup we show that LIMK1 is depleted if SM311 is added in excess but also identified two additional kinase off-targets that required further profiling.
Project description:Modulation of protein-protein interactions with small molecules represents an emerging area of interest in drug discovery, enabling new therapeutic paradigms unprecedented with other drug classes such as catalytic enzyme inhibitors. Immunomodulatory or PROTAC drugs are a prime example for proximity-induced pharmacology where in the case of multiple myeloma, degradation of oncogenic transcription factors is achieved via recruitment of an E3 ligase complex. This EUbOPEN project is a collaboration between ETHZ and UTOR which aims to identify target protein proximity induced by USP21 inhibitors.