CBK288679 (CBK79) is a novel compound that impairs both protein degradation by the ubiquitin-proteasome system (UPS) and autophagy.CBK79 inhibits cell viability of MelJuSo Ub-YFP cells with 72h IC50 of 0.22 uM, CBK79-inflicted cell death was caspase-independent.CBK79 causes accumulation of ubiquitin-dependent and -independent proteasome substrates.CBK79 induces non-canonical lipidation of MAP1LC3B/LC3B (microtubule-associated protein 1 light chain 3 beta) that requires ATG16L1 but is independent of the ULK1 and class III phosphatidylinositol 3-kinase (PtdIns3K) complexes.CBK79 (10 uM) induces proteotoxic stress and the heat shock response in HOS GFP-LC3B cells.CBK79 has unique features as it inhibits both ubiquitin-dependent and -independent degradation of short-lived proteins by the UPS, as well as the degradation of long-lived proteins by autophagy.
