Identification of Common Biological Pathways and Drug Targets Across Multiple Respiratory Viruses Based on Human Host Gene Expression Analysis

Smith, Steven B.; Dampier, William; Tozeren, Aydin; Brown, James R.; Magid-Slav, Michal

Parkin (PARK2) is an E3-ubiqutin ligase associated with the progression of the neurodegenerative disorder Parkinson's disease. [47] . As a central hub protein in the Parkin-UPS pathway, PARK2 ubiquinates proteins encoded by septin 5 (SEPT5) [48] , tubulin alpha and beta [49] , and the glycosylated form of synuclein, alpha (SNCA) [50] for degradation by the 26S proteasome. PARK2 also ubiquinates synuclein, alpha interacting protein (SNCAIP) for regulation of SNCA [51] , interacts with STIP1 homology and U-box containing protein 1 E3 ubiquitin protein ligase (STUB1) to enhance ubiquitination of G proteincoupled receptor 37 (GPR37), [52] (which associates with F-box and WD repeat domain containing 7 (FBXW7)), and cullin 1 (CUL1) to ubiquitinate cyclin E [53] . PARK2 is deactivated by protolytic cleavage by CASP1 and Caspase 8 (CASP 8) [54] and can be activated by either heat shock protein 70kD (HSPA4) or STUB1 [52] .