Ubiquitin modification of many cellular proteins targets them for proteasomal degradation, but in addition can also serve non-proteolytic functions. Over the last years, a significant progress has been made in our understanding of how modification of the substrates of the ubiquitin system is regulated. However, little is known on how the ubiquitin system that is comprised of ∼1500 components is regulated. Here, we discuss how the biggest subfamily within the system, that of the E3 ubiquitin ligases that endow the system with its high specificity towards the numerous substrates, is regulated and in particular via self-regulation mediated by ubiquitin modification. Ligases can be targeted for degradation in a self-catalyzed manner, or through modification mediated by an external ligase(s). In addition, non-proteolytic functions of self-ubiquitination, for example activation of the ligase, of E3s are discussed.
c-Cbl is transiently tyrosine-phosphorylated, ubiquitinated, and membrane-targeted following CSF-1 stimulation of macrophages.
Siah-1 N-terminal RING domain is required for proteolysis function, and C-terminal sequences regulate oligomerization and binding to target proteins
The Elongin BC complex interacts with the conserved SOCS-box motif present in members of the SOCS, ras, WD-40 repeat, and ankyrin repeat families
Association of p19(ARF) with Mdm2 inhibits ubiquitin ligase activity of Mdm2 for tumor suppressor p53
Signaling by proinflammatory cytokines: oligomerization of TRAF2 and TRAF6 is sufficient for JNK and IKK activation and target gene induction via an amino-terminal effector domain
Ubiquitin ligase activity and tyrosine phosphorylation underlie suppression of growth factor signaling by c-Cbl/Sli-1
The F-box protein Skp2 is a ubiquitylation target of a Cul1-based core ubiquitin ligase complex: evidence for a role of Cul1 in the suppression of Skp2 expression in quiescent fibroblasts
The RING heterodimer BRCA1-BARD1 is a ubiquitin ligase inactivated by a breast cancer-derived mutation
The tumor autocrine motility factor receptor, gp78, is a ubiquitin protein ligase implicated in degradation from the endoplasmic reticulum
A molecular basis for stabilization of the von Hippel-Lindau (VHL) tumor suppressor protein by components of the VHL ubiquitin ligase.
Interaction between two ubiquitin-protein isopeptide ligases of different classes, CBLC and AIP4/ITCH.
Prophase destruction of Emi1 by the SCF(betaTrCP/Slimb) ubiquitin ligase activates the anaphase promoting complex to allow progression beyond prometaphase
Ligand-induced lysosomal epidermal growth factor receptor (EGFR) degradation is preceded by proteasome-dependent EGFR de-ubiquitination.
The BRCA1/BARD1 heterodimer assembles polyubiquitin chains through an unconventional linkage involving lysine residue K6 of ubiquitin.
Determination of cell survival by RING-mediated regulation of inhibitor of apoptosis (IAP) protein abundance
Sensing of Lys 63-linked polyubiquitination by NEMO is a key event in NF-kappaB activation [corrected
Alix facilitates the interaction between c-Cbl and platelet-derived growth factor beta-receptor and thereby modulates receptor down-regulation
Site-specific Lys-63-linked tumor necrosis factor receptor-associated factor 6 auto-ubiquitination is a critical determinant of I kappa B kinase activation
The polycomb protein Ring1B generates self atypical mixed ubiquitin chains required for its in vitro histone H2A ligase activity
Regulation of the Drosophila ubiquitin ligase DIAP1 is mediated via several distinct ubiquitin system pathways
Targeted inactivation of Mdm2 RING finger E3 ubiquitin ligase activity in the mouse reveals mechanistic insights into p53 regulation
The ubiquitin E3 ligase MARCH7 is differentially regulated by the deubiquitylating enzymes USP7 and USP9X
Regulation of Nedd4-2 self-ubiquitination and stability by a PY motif located within its HECT-domain
Structural insights into NEDD8 activation of cullin-RING ligases: conformational control of conjugation
Nedd4 augments the adaptive immune response by promoting ubiquitin-mediated degradation of Cbl-b in activated T cells
CYLD: a tumor suppressor deubiquitinase regulating NF-kappaB activation and diverse biological processes
PKC-theta modulates the strength of T cell responses by targeting Cbl-b for ubiquitination and degradation
Targeting of gp78 for ubiquitin-mediated proteasomal degradation by Hrd1: cross-talk between E3s in the endoplasmic reticulum
Lysine 63-linked polyubiquitination of TAK1 at lysine 158 is required for tumor necrosis factor alpha- and interleukin-1beta-induced IKK/NF-kappaB and JNK/AP-1 activation
Regulation of the polycomb protein Ring1B by self-ubiquitination or by E6-AP may have implications to the pathogenesis of Angelman syndrome
Exploring a new frontier in cancer treatment: targeting the ubiquitin and ubiquitin-like activating enzymes
Newly discovered viral E3 ligase pK3 induces endoplasmic reticulum-associated degradation of class I major histocompatibility proteins and their membrane-bound chaperones.
Systematic analysis of dimeric E3-RING interactions reveals increased combinatorial complexity in human ubiquitination networks.
Comprehensive analysis of the rice RING E3 ligase family reveals their functional diversity in response to abiotic stress
Characterization of the Arabidopsis thaliana E3 ubiquitin-ligase AtSINAL7 and identification of the ubiquitination sites
Tight, cell type-specific control of LNX expression in the nervous system, at the level of transcription, translation and protein stability
Tripartite motif ligases catalyze polyubiquitin chain formation through a cooperative allosteric mechanism.
Self-clearance mechanism of mitochondrial E3 ligase MARCH5 contributes to mitochondria quality control.
RNF12 promotes p53-dependent cell growth suppression and apoptosis by targeting MDM2 for destruction
The E3 ubiquitin-ligase SEVEN IN ABSENTIA like 7 mono-ubiquitinates glyceraldehyde-3-phosphate dehydrogenase 1 isoform in vitro and is required for its nuclear localization in Arabidopsis thaliana
TCTP increases stability of hypoxia-inducible factor 1α by interaction with and degradation of the tumour suppressor VHL
Mitochondrial E3 ubiquitin ligase 1: A key enzyme in regulation of mitochondrial dynamics and functions
Genomic instability causes HGF gene activation in colon cancer cells, promoting their resistance to necroptosis
PUB22 and PUB23 U-BOX E3 ligases directly ubiquitinate RPN6, a 26S proteasome lid subunit, for subsequent degradation in Arabidopsis thaliana
MSL2 combines sensor and effector functions in homeostatic control of the Drosophila dosage compensation machinery
The chimeric ubiquitin ligase SH2-U-box inhibits the growth of imatinib-sensitive and resistant CML by targeting the native and T315I-mutant BCR-ABL
The LXR-IDOL axis defines a clathrin-, caveolae-, and dynamin-independent endocytic route for LDLR internalization and lysosomal degradation.
Post-translational modification profiling - A novel tool for mapping the protein modification landscape in cancer
Interaction profiling of RNA-binding ubiquitin ligases reveals a link between posttranscriptional regulation and the ubiquitin system
The Cullin-3-Rbx1-KCTD10 complex controls endothelial barrier function via K63 ubiquitination of RhoB
MPSR1 is a cytoplasmic PQC E3 ligase for eliminating emergent misfolded proteins in Arabidopsis thaliana
Active site-targeted covalent irreversible inhibitors of USP7 impair the functions of Foxp3+ T-regulatory cells by promoting ubiquitination of Tip60
Ubiquitin-mediated regulation of the E3 ligase GP78 by MGRN1 in trans affects mitochondrial homeostasis
An E3 ubiquitin ligase from Nicotiana benthamiana targets the replicase of Bamboo mosaic virus and restricts its replication
Grain width 2 (GW2) and its interacting proteins regulate seed development in rice (Oryza sativa L.)
The Steroidogenic Enzyme AKR1C3 Regulates Stability of the Ubiquitin Ligase Siah2 in Prostate Cancer Cells.
Regulation of the anaphase promoting complex/cyclosome by the degradation of its unassembled catalytic subunit, Apc11
The mammalian CTLH complex is an E3 ubiquitin ligase that targets its subunit muskelin for degradation
A novel UBE3A sequence variant identified in eight related individuals with neurodevelopmental delay, results in a phenotype which does not match the clinical criteria of Angelman syndrome
Dynamics of ubiquitin-mediated signalling: insights from mathematical modelling and experimental studies
A Conserved C-terminal Element in the Yeast Doa10 and Human MARCH6 Ubiquitin Ligases Required for Selective Substrate Degradation.
The Catalytically Inactive Mutation of the Ubiquitin-Conjugating Enzyme CDC34 Affects its Stability and Cell Proliferation
RING-Domain E3 Ligase-Mediated Host-Virus Interactions: Orchestrating Immune Responses by the Host and Antagonizing Immune Defense by Viruses
Arabidopsis BRUTUS-LIKE E3 ligases negatively regulate iron uptake by targeting transcription factor FIT for recycling
Expression profiling of WD40 family genes including DDB1- and CUL4- associated factor (DCAF) genes in mice and human suggests important regulatory roles in testicular development and spermatogenesis
Actin Cytoskeletal Organization in Drosophila Germline Ring Canals Depends on Kelch Function in a Cullin-RING E3 Ligase
Homologous U-box E3 Ubiquitin Ligases OsPUB2 and OsPUB3 Are Involved in the Positive Regulation of Low Temperature Stress Response in Rice (Oryza sativa L.)
Post-translational Down-regulation of Melanoma Antigen-A11 (MAGE-A11) by Human p14-ARF Tumor Suppressor.
Acetylation drives hepatocyte nuclear factor 1β stability by blocking proteasome-mediated degradation
Glycine Regulates Neural Stem Cell Proliferation During Development via Lnx1-Dependent Notch Signaling
E3 ubiquitin ligase RNF126 promotes cancer cell proliferation by targeting the tumor suppressor p21 for ubiquitin-mediated degradation
Ubiquitin chain specific auto-ubiquitination triggers sustained oscillation, bistable switches and excitable firing
Overlapping Molecular Pathways Leading to Autism Spectrum Disorders, Fragile X Syndrome, and Targeted Treatments
Haploinsufficiency of Casitas B-Lineage Lymphoma Augments the Progression of Colon Cancer in the Background of Adenomatous Polyposis Coli Inactivation.
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