Ubiquitination is a key post-translational modification in the regulation of numerous biological processes in eukaryotes. The primary roles of ubiquitination are thought to be the triggering of protein degradation and the regulation of signal transduction. During protein ubiquitination, substrate specificity is mainly determined by E3 ubiquitin ligase (E3). Although more than 600 genes in the h...

OBJECTIVES Ubiquitin E3 ligase-mediated protein degradation regulates osteoblast function. Itch, an E3 ligase, affects numerous cell functions by regulating ubiquitination and proteasomal degradation of related proteins. However, the Itch-related cellular and molecular mechanisms by which osteoblast differentiation and function are elevated during bone fracture repair are as yet unknown. METH...

Nedd4-family E3 ubiquitin ligases regulate signaling in intracellular pathways that control cancer, blood pressure, iron metabolism, and inflammation. These E3 ligases are catalytically active, and share a highly conserved, modular architecture. How Nedd4 family members are differentially regulated, despite their high degree of homology, is unclear. A regulatory mechanism that maintains an inac...

•High-glucose-induced ROS promotes phosphorylation of AMPKα at S485/491 by AKT•Phosphorylation is required for recruitment E3 ligase MG53•MG53 mediates skeletal muscle ubiquitination and subsequent degradation•High glucose also deactivates inducing disassociation from LKB1 As a master regulator metabolism, AMP-activated protein kinase (AMPK) activated upon energy shortage but suppressed overnut...

A number of recent papers on the WWP2 E3 ubiquitin ligase together with two novel WWP2 isoforms have revealed important biological insight and disease-specific functions, and also impacted on our understanding of ubiquitin ligases in cell cycle regulation, apoptosis and differentiation. Gene knockout studies suggest a developmental role for WWP2 in chondrogenesis via mechanisms involving cartil...

Covalent attachment of one or more ubiquitin molecules to protein substrates governs numerous eukaryotic cellular processes including apoptosis, cell division and immune response. Ubiquitylated proteins can be targeted for degradation but ubiquitylation also mediates processes such as protein-protein interactions and cell signalling, depending on the type of ubiquitin conjugation. Ubiquitin lig...

Krüppel-like factor 5 (KLF5) regulates multiple biologic processes. Its function in tumorigenesis appears contradictory though, showing both tumor suppressor and tumor promoting activities. In this study, we examined whether and how Klf5 functions in prostatic tumorigenesis using mice with prostate-specific deletion of Klf5 and phosphatase and tensin homolog (Pten), both of which are frequently...