Cullin-RING E3 ubiquitin ligases

A predominant form of eukaryotic regulation involves the dynamic linkage and removal of ubiquitin (and structurally-related ubiquitin-like proteins, UBLs) to control the half-lives, subcellular location, conformation, and other properties of most intracellular proteins. The specificity of ubiquitylation depends on a vast collection of E3 ligase enzymes that modify particular protein substrates at the right time and place in a cell. With more than 200 different family members in humans, and even more in plants and other organisms, the largest E3 ligase family comprises the modular, multisubunit Cullin-RING ligases (CRLs). CRLs regulate virtually every facet of cell biology, including the cell cycle, DNA repair, stress responses, signaling, immunity, circadian rhythms, and a plethora of other pathways. Meanwhile defects in specific CRL subunits underlie numerous diseases including hypertension, neurodegenerative disorders, developmental defects, cancers, and immune system dysfunction, and many bacterial and viral pathogens subvert and/or hijack CRL pathways to promote infection and evade host defense systems. To understand this immense regulation, a major focus of our lab is to identify pathways and determine molecular mechanisms underlying CRL activities. I will present an update of our latest research on mechanisms regulating and/or regulated by cullin-RING E3 ubiquitin ligases.