title: Regulating the Regulators: Recent Revelations in the Control of E3 Ubiquitin Ligases.
abstract: Since its discovery as a post-translational signal for protein degradation, our understanding of ubiquitin (Ub) has vastly evolved. Today, we recognize that the role of Ub signaling is expansive and encompasses diverse processes including cell division, the DNA damage response, cellular immune signaling, and even organismal development. With such a wide range of functions comes a wide range of regulatory mechanisms that control the activity of the ubiquitylation machinery. Ub attachment to substrates occurs through the sequential action of three classes of enzymes, E1s, E2s, and E3s. In humans, there are 2 E1s, ∼ 35 E2s, and hundreds of E3s that work to attach Ub to thousands of cellular substrates. Regulation of ubiquitylation can occur at each stage of the stepwise Ub transfer process, and substrates can also impact their own modification. Recent studies have revealed elegant mechanisms that have evolved to control the activity of the enzymes involved. In this minireview, we highlight recent discoveries that define some of the various mechanisms by which the activities of E3-Ub ligases are regulated.
authors.affiliation: From the Department of Biochemistry, University of Washington, Seattle, Washington 98195-7742.
authors.forename: Vinayak
authors.initials: V
authors.lastname: Vittal
authors.affiliation: From the Department of Biochemistry, University of Washington, Seattle, Washington 98195-7742.
authors.forename: Mikaela D
authors.initials: MD
authors.lastname: Stewart
authors.affiliation: From the Department of Biochemistry, University of Washington, Seattle, Washington 98195-7742.
authors.forename: Peter S
authors.initials: PS
authors.lastname: Brzovic
authors.affiliation: From the Department of Biochemistry, University of Washington, Seattle, Washington 98195-7742 klevit@uw.edu.
authors.forename: Rachel E
authors.identifier: http://orcid.org/0000-0002-3476-969X
authors.initials: RE
authors.lastname: Klevit
mesh_terms: D000818:Animals; D044842:Cullin Proteins / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D025801:Ubiquitin / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000737:chemistry / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: D044842:Cullin Proteins; D025801:Ubiquitin; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein
keywords: E3 ubiquitin ligase; HECT; RING; cullin; parkin; ubiquitin; ubiquitin ligase; ubiquitin regulation; ubiquitylation (ubiquitination)