Journal ArticleDOI
RING Domain E3 Ubiquitin Ligases
Reads0
Chats0
TLDR
RING E3s have been linked to the control of many cellular processes and to multiple human diseases, and knowledge of the physiological partners, biological functions, substrates, and mechanism of action for most RING E 3s remains at a rudimentary stage.Abstract:
E3 ligases confer specificity to ubiquitination by recognizing target substrates and mediating transfer of ubiquitin from an E2 ubiquitinconjugating enzyme to substrate. The activity of most E3s is specified by a RING domain, which binds to an E2∼ubiquitin thioester and activates discharge of its ubiquitin cargo. E2-E3 complexes can either monoubiquitinate a substrate lysine or synthesize polyubiquitin chains assembled via different lysine residues of ubiquitin. These modifications can have diverse effects on the substrate, ranging from proteasome-dependent proteolysis to modulation of protein function, structure, assembly, and/or localization. Not surprisingly, RING E3mediated ubiquitination can be regulated in a number of ways. RING-based E3s are specified by over 600 human genes, surpassing the 518 protein kinase genes. Accordingly, RING E3s have been linked to the control of many cellular processes and to multiple human diseases. Despite their critical importance, our knowledge of the physiological partners, biological functions, substrates, and mechanism of action for most RING E3s remains at a rudimentary stage.read more
Citations
More filters
Journal ArticleDOI
The Ubiquitin Code
David Komander,Michael Rape +1 more
TL;DR: The structure, assembly, and function of the posttranslational modification with ubiquitin, a process referred to as ubiquitylation, controls almost every process in cells.
Journal ArticleDOI
Classification of intrinsically disordered regions and proteins.
Robin van der Lee,Robin van der Lee,Marija Buljan,Benjamin Lang,Robert J. Weatheritt,Gary W. Daughdrill,A. Keith Dunker,Monika Fuxreiter,Julian Gough,Joerg Gsponer,David T. Jones,Philip M. Kim,Richard W. Kriwacki,Christopher J. Oldfield,Rohit V. Pappu,Peter Tompa,Peter Tompa,Vladimir N. Uversky,Vladimir N. Uversky,Peter E. Wright,M. Madan Babu +20 more
TL;DR: Characterization of unannotated and uncharacterized protein segments is expected to lead to the discovery of novel functions as well as provide important insights into existing biological processes and is likely to shed new light on molecular mechanisms of diseases that are not yet fully understood.
Journal ArticleDOI
Lenalidomide Causes Selective Degradation of IKZF1 and IKZF3 in Multiple Myeloma Cells
Jan Krönke,Namrata D. Udeshi,Anupama Narla,Peter V. Grauman,Slater N. Hurst,Marie McConkey,Tanya Svinkina,Dirk Heckl,Eamon Comer,Xiaoyu Li,Christie Ciarlo,Emily C. Hartman,Nikhil C. Munshi,Monica Schenone,Stuart L. Schreiber,Steven A. Carr,Benjamin L. Ebert,Benjamin L. Ebert +17 more
TL;DR: Using quantitative proteomics, it is found that lenalidomide causes selective ubiquitination and degradation of two lymphoid transcription factors, IKZF1 and IKzF3, by the CRBN-CRL4 ubiquitin ligase, which are essential transcription factors in multiple myeloma.
Journal ArticleDOI
MDM2, MDMX and p53 in oncogenesis and cancer therapy.
TL;DR: This Review highlights the progress made and pitfalls encountered as the field continues to search for MDM-targeted antitumour agents.
Journal ArticleDOI
The SUMO pathway: emerging mechanisms that shape specificity, conjugation and recognition.
TL;DR: A better understanding of SUMO regulatory mechanisms will lead to improved approaches for analysing the function ofsumO and substrate conjugation in distinct cellular pathways.
References
More filters
Journal ArticleDOI
Targeting of HIF-alpha to the von Hippel-Lindau Ubiquitylation Complex by O2-Regulated Prolyl Hydroxylation
Panu Jaakkola,David R. Mole,Ya-Min Tian,Michael I. Wilson,Janine Gielbert,Simon J. Gaskell,Alex von Kriegsheim,Holger F. Hebestreit,Mridul Mukherji,Christopher J. Schofield,Patrick H. Maxwell,Christopher W. Pugh,Peter J. Ratcliffe +12 more
TL;DR: It is shown that the interaction between human pVHL and a specific domain of the HIF-1α subunit is regulated through hydroxylation of a proline residue by an enzyme the authors have termed Hif-α prolyl-hydroxylase (HIF-PH).
Journal ArticleDOI
HIFα Targeted for VHL-Mediated Destruction by Proline Hydroxylation: Implications for O2 Sensing
Mircea Ivan,Keiichi Kondo,Haifeng Yang,William Y. Kim,Jennifer Valiando,Michael Ohh,Adrian Salic,John M. Asara,William S. Lane,William G. Kaelin,William G. Kaelin +10 more
TL;DR: It is found that human pVHL binds to a short HIF-derived peptide when a conserved proline residue at the core of this peptide is hydroxylated, which may play a key role in mammalian oxygen sensing.
Journal ArticleDOI
Mechanisms underlying ubiquitination.
TL;DR: Recent findings reveal that all known E3s utilize one of just two catalytic domains--a HECT domain or a RING finger--and crystal structures have provided the first detailed views of an active site of each type.
Journal ArticleDOI
Function and regulation of cullin-RING ubiquitin ligases.
TL;DR: This review focuses on the composition, regulation and function of cullin–RING ligases, and describes how these enzymes can be characterized by a set of general principles.
Journal ArticleDOI
Recognition of the polyubiquitin proteolytic signal.
TL;DR: The properties of the substrates studied here implicate substrate unfolding as a kinetically dominant step in the proteolysis of properly folded proteins, and suggest that extraproteasomal chaperones are required for efficient degradation of certain proteasome substrates.