| 2023 |
Cryo-EM structures of human Elongin (ELOA-ELOB-ELOC) bound to transcribing RNA polymerase II show that ELOB-ELOC form a heterodimer anchored to ELOA, which binds the RPB2 side of Pol II; ELOA contains a 'latch' that contacts the Pol II bridge helix/funnel region to allosterically regulate the polymerase active center, and this latch is required for elongation-stimulatory activity but not for Pol II binding. |
Cryo-EM structure determination with functional validation (latch mutants tested for elongation stimulation and Pol II binding) |
Nature structural & molecular biology |
High |
37932450
|
| 2011 |
HIV-1 Vif recruits CBF-β to an E3 ubiquitin ligase complex containing CUL5, ELOB, ELOC, and RBX2; reconstitution of the six-protein complex (Vif-CBF-β-CUL5-ELOB-ELOC-RBX2) elicits specific polyubiquitination of APOBEC3G but not APOBEC3A. CBF-β knockdown prevents Vif-mediated APOBEC3G degradation. |
Affinity tag/purification mass spectrometry, recombinant protein reconstitution, in vitro ubiquitination assay, RNA knockdown and genetic complementation |
Nature |
High |
22190037
|
| 2014 |
Crystal structure of the Vif-CBF-β-CUL5-ELOB-ELOC pentameric complex reveals that Vif organizes the complex through two domains: an α/β domain binding CBF-β (exclusive with RUNX1 binding) and an α-domain that cooperatively interacts with ELOC and CUL5, mimicking SOCS2. A unique zinc-finger motif of Vif stabilizes the α-domain conformation important for CUL5 interaction. |
X-ray crystallography |
Nature |
High |
24402281
|
| 2004 |
Vif targets APOBEC3G for degradation by forming an SCF-like E3 ubiquitin ligase containing CUL5, ELOB, and ELOC through a SOCS-box that binds ELOC. Serine phosphorylation in the BC-box motif negatively regulates Vif binding to ELOC. Vif autoubiquitination in the assembled Vif-CUL5 complex requires an intact SOCS-box. |
Co-immunoprecipitation, in vitro and in vivo ubiquitination assays, mutagenesis, phosphorylation analysis |
Genes & development |
High |
15574592
|
| 2010 |
Vif binds to ELOB-ELOC at two locations via an induced-folding mechanism: the established BC-box of Vif binds ELOC, and a conserved Pro-Pro-Leu-Pro motif of Vif interacts with the C-terminal domain of ELOB. Both interactions induce structural changes in Vif's SOCS-box and ELOB-ELOC. The PPLP-ELOB interaction is necessary for functional ligase complex formation. |
Purified protein direct binding assays, isothermal titration calorimetry, NMR spectroscopy, cell-based functional assays |
PLoS pathogens |
High |
20532212
|
| 2013 |
NMR solution structure of the Vif SOCS-box bound to ELOB-ELOC reveals that Vif's SOCS-box has one α-helical domain followed by a β-sheet fold (distinct from other SOCS proteins), binds primarily to ELOC by hydrophobic interactions, and the proline-rich motif mediates a direct but weak interaction with residues 101-104 of ELOB, inducing a conformational change from unstructured to structured. |
NMR spectroscopy, biophysical characterization |
Open biology |
High |
24225024
|
| 2012 |
CBF-β interacts directly with full-length Vif; association of Vif with ELOB-ELOC greatly increases solubility of full-length Vif; a stable Vif-CBF-β-ELOB-ELOC complex was purified and shown to bind purified CUL5. ELOB-ELOC but not CBF-β greatly enhances folding of full-length Vif in E. coli. |
Protein co-expression and purification, direct binding assays, solubility assays |
PloS one |
Medium |
22479405
|
| 2012 |
CBF-β increases the affinity of CUL5 for the Vif/ELOB/ELOC complex: isothermal calorimetry shows CUL5 binds Vif(1-192)/ELOB/ELOC/CBF-β with Kd ~5 nM versus ~327 nM for Vif(95-192)/ELOB/ELOC (which cannot bind CBF-β). CBF-β prestabilizes Vif, strengthening Vif's C-terminal Zn2+-binding motif interaction with CUL5. |
Isothermal titration calorimetry, heat capacity analysis |
Biochemistry |
Medium |
23098073
|
| 2013 |
ELOB positively affects CBF-β recruitment to Vif: knockdown of endogenous ELOB or overexpression of an ELOB mutant lacking the 34-residue C-terminal tail (EBΔC34) impairs the Vif-CBF-β interaction. ELOB overexpression stabilizes Vif/VifΔSLQ/VifΔPPL through a region between residues 9 and 14 of ELOB. |
siRNA knockdown, co-immunoprecipitation, mutant overexpression, E. coli co-expression |
Retrovirology |
Medium |
23988114
|
| 2020 |
ELOB (as a PRC2-associated subunit) is enriched at lineage specifier gene promoters during the G1 phase of the cell cycle in mouse embryonic stem cells, while PRC2 catalytic subunits (Ezh2, Jarid2) are enriched during S/G2 phases. This differential recruitment across cell cycle is linked to changes in RNA synthesis and RNA polymerase II binding. |
ChIP-seq, cell cycle synchronization, live-cell imaging, transcriptional analysis |
Science advances |
Medium |
32181346
|
| 2020 |
Cryo-EM structure of ASB9-ELOB-ELOC bound to substrate (creatine kinase) and CUL5-RBX2 reveals that ELOB-ELOC acts as a hinge between ASB9 and CUL5, transmitting long-range allosteric crosstalk from the substrate through CUL5 to RBX2. HDX-MS confirms ELOB-ELOC provides conformational flexibility while ASB9 and CUL5 behave as rigid rods. |
Cryo-EM, hydrogen-deuterium exchange mass spectrometry (HDX-MS) |
Nature communications |
High |
32513959
|
| 2014 |
BIV Vif recruits ELOB-ELOC together with CUL2 and RBX1 (not CUL5 or CBF-β) to form a CRL2 E3 ubiquitin ligase complex; siRNA knockdown of ELOB inhibits BIV Vif-mediated degradation of bovine APOBEC3 proteins. BC-box mutation in BIV Vif (SLQ-AAA) abolishes ELOB-ELOC interaction and A3 degradation. |
Co-immunoprecipitation, siRNA knockdown, mutagenesis, ubiquitination assays |
Journal of virology |
Medium |
25142583
|
| 2014 |
MVV Vif also recruits ELOB-ELOC (together with CUL5) in a CBF-β-independent manner to degrade ovine APOBEC3Z2-Z3; BC-box mutations in MVV Vif disrupt ELOB-ELOC binding and abolish A3 degradation. |
Co-immunoprecipitation, mutagenesis, dominant-negative mutants |
Retrovirology |
Medium |
25213124
|
| 2007 |
Adenoviral protein Gam1 recruits SAE1/SAE2 (SUMO E1) into CUL2/5-ELOB-ELOC-ROC1 ubiquitin ligase complexes via its SOCS domain, leading to SAE1 ubiquitylation and degradation; this inactivates sumoylation. ELOB is thus a component of Gam1-recruited CUL-RING ligases mediating viral antagonism of SUMO pathway. |
Co-immunoprecipitation, in vitro and in vivo ubiquitination assays, knockdown/rescue |
The Journal of biological chemistry |
Medium |
17392274
|
| 2021 |
ELOB is a component of the CUL2-RBX1-ELOB E3 ligase (CRL2Prame) complex that mediates ubiquitination and proteasomal degradation of p14/ARF. Immunoprecipitation and in vivo ubiquitination assays established Cullin2-RBX1-ELOB assembly, with Prame as the substrate receptor recognizing p14/ARF. |
Co-immunoprecipitation, in vivo ubiquitination assay, siRNA knockdown |
Cell death and differentiation |
Medium |
33504946
|
| 2024 |
ELOB, as the core element of the CUL2-RBX1-ELOB E3 ligase (CRL2) complex, regulates ubiquitination and proteasomal degradation of p14/ARF in breast cancer cells; ELOB knockdown suppresses proliferation, rescued by simultaneous p14/ARF knockdown. |
Co-immunoprecipitation, in vivo ubiquitination assay, siRNA knockdown, in vivo xenograft |
Cell biology and toxicology |
Medium |
38653919
|
| 2023 |
ELOB (as part of the Elongin BC heterodimer) negatively regulates AXL receptor tyrosine kinase expression in melanoma; CRISPR screen, followed by functional validation, shows ELOB interacts with AXL through ELOB directly, contributing to proteasomal AXL turnover. This regulation is independent of hypoxia/VHL. |
FACS-based whole-genome CRISPR-Cas9 screen, Co-immunoprecipitation, proteasome inhibition assays |
Molecular cancer research |
Medium |
36753617
|
| 2018 |
ANKRD9 forms a CUL5-ELOB-ELOC-RNF7 cullin-RING E3 ligase complex (not CUL2) and functions as its substrate receptor. This complex ubiquitinates IMPDH isoforms (IMPDH1 and IMPDH2) for proteasomal degradation; ubiquitination requires ANKRD9 presence. |
Quantitative proteomics, Co-IP, complex reconstitution, in vitro ubiquitination assay |
Biochimica et biophysica acta. Molecular basis of disease |
Medium |
30293565
|
| 2024 |
ASB1 interacts with ELOB to assemble an E3 ubiquitin ligase complex that promotes K48-linked ubiquitination of sulfide-quinone oxidoreductase (SQOR) at residues K207 and K344, triggering proteasomal degradation and controlling H2S homeostasis during spermiogenesis. |
Co-immunoprecipitation, in vivo ubiquitination assay, Asb1 knockout mouse model, site-directed mutagenesis |
Redox biology |
Medium |
39733518
|
| 2024 |
ZSWIM4 interacts with ELOB and ELOC (identified by SILAC proteomics) and forms a CUL2-RING ubiquitin ligase complex with ELOB-ELOC to promote ubiquitination and nuclear degradation of SMAD1, attenuating BMP signaling during Xenopus embryonic patterning. |
SILAC proteomics, Co-immunoprecipitation, in vivo ubiquitination assay, Xenopus loss-of-function/gain-of-function |
EMBO reports |
Medium |
38177922
|
| 2023 |
TULP4 forms a novel E3 ubiquitin ligase through interaction with CUL5-ELOB-ELOC-RNF7 complex; schizophrenia-associated TULP4 variants affect binding of TULP4 to CUL5. Tulp4 knockdown delays neuronal migration in mice. |
Co-immunoprecipitation, whole-exome sequencing, in utero knockdown, behavioral assays |
CNS neuroscience & therapeutics |
Low |
37650344
|
| 2023 |
USP51 directly binds ELOC and forms a larger complex with the VHL E3 ligase (USP51/VHL/CUL2/ELOB/ELOC/RBX1); within this complex USP51 deubiquitinates HIF1A to stabilize it. SUMOylation of ELOC at K32 inhibits USP51 binding, while SENP1-mediated deSUMOylation of ELOC promotes USP51 association. |
Co-immunoprecipitation, in vivo deubiquitination assay, SUMOylation assay, siRNA knockdown |
Cell death and differentiation |
Medium |
37816999
|
| 2023 |
Cryo-EM structure of HIV-1 Vif in complex with APOBEC3H, CBF-β, CUL5, ELOB, and ELOC reveals that Vif nucleates the complex by directly binding all four human proteins; ELOB-ELOC serve as adaptor components within this structural assembly. |
Cryo-EM structure determination, functional mutagenesis |
Nature communications |
High |
37640699
|
| 2025 |
Cryo-EM structure (3.6 Å) of chimpanzee APOBEC3H-Vif-CBF-β-ELOB-ELOC complex demonstrates that ELOB and ELOC are integral structural components of the CUL5 E3 ligase complex; ubiquitination by this complex occurs specifically at two lysine residues on the Vif-proximal A3H protomer. |
Cryo-EM structure determination, in vitro ubiquitination assay with site mapping |
Nature communications |
High |
40593686
|
| 2023 |
A peptide mimicking the BC-box of EPOP (PRC2-associated protein) binds ELOB-ELOC with sub-nanomolar affinity (Kd = 0.46 nM) and blocks ELOB-ELOC association with BC-box-containing interaction partners both in vitro and in cells, inducing apoptosis in cancer cells and perturbing gene expression. |
In vitro binding assay (fluorescence polarization/ITC), cellular co-immunoprecipitation displacement, viability/apoptosis assays, RNA-seq |
Cell chemical biology |
Medium |
37354906
|
| 2025 |
Rotavirus NSP1 contains a BC-box motif that mediates interaction with the Elongin BC complex (ELOB-ELOC); CRISPR knockout or siRNA knockdown of TCEB2 (ELOB) substantially prevents NSP1-mediated IRF3 degradation. Elongin BC also stabilizes other viral BC-box-containing innate immune antagonists (pestiviral N proteases, adenovirus E4orf6), functioning not only as ubiquitin ligase adaptor but as a stabilizing factor for viral proteins. |
CRISPR knockout, siRNA knockdown, recombinant virus BC-box mutagenesis, IRF3 degradation assay, interferon response measurement |
Proceedings of the National Academy of Sciences of the United States of America |
High |
42234532
|
| 2018 |
JDV Vif recruits ELOB-ELOC (together with CUL2 and RBX1, not CBF-β) via a BC-box motif (T149LQ151) to form an E3 ubiquitin ligase that degrades bovine APOBEC3 proteins. |
Co-immunoprecipitation, mutagenesis, degradation assays |
Virology |
Low |
29653302
|
| 2016 |
The C-terminal cytoplasmic tail of Patched1 (Ptc1 ICD7) interacts with components of a CUL2-based E3 ligase complex including TCEB2 (ELOB), TCEB1 (ELOC), ZYG11B, and CUL2, identified by mass spectrometry; CUL2 knockdown abolishes Shh-induced osteoblast differentiation. |
Mass spectrometry identification, co-immunoprecipitation, CUL2 knockdown |
Molecular and cellular biochemistry |
Low |
26885983
|
| 2015 |
TCEB2 (ELOB) plays a role in HIF-1α degradation; TCEB2 overexpression promotes HIF-1α degradation and suppresses VEGF-A expression in ovarian cancer cells. TCEB2-overexpressing cells elevate IL-8 as a compensatory angiogenesis signal. |
Overexpression in xenograft models, gene expression analysis, Western blot |
Oncology reports |
Low |
26531153
|
| 2024 |
TCEB2 mediates Slit2 K63-linked ubiquitination degradation in TNBC by interacting with NEDD4 (via Co-IP); TCEB2 knockdown reduces TNBC cell growth, migration, invasion, and M2 macrophage polarization, which is rescued by Slit2 knockdown. |
Co-immunoprecipitation, ubiquitin-based IP assay, siRNA knockdown, in vivo xenograft |
Translational oncology |
Medium |
41014880
|
| 2024 |
ASB9 assembles a testis-specific CRL complex (TNP2-ASB9-ELOB-ELOC-CUL5-RBX1) that mediates ubiquitin-dependent degradation of TNP2 to facilitate histone-to-protamine transition; ASB9 deficiency in mice causes TNP2 retention and male infertility. |
Co-immunoprecipitation, in vivo ubiquitination assay, ASB9 knockout mouse model |
Proceedings of the National Academy of Sciences of the United States of America |
Medium |
41915740
|
| 2026 |
ELOB knockout inhibits diffuse midline glioma (DMG) cell proliferation in vitro and tumor growth in xenograft models; ELOB binding sites are enriched in H3K27M oncohistone-containing genomic regions, and ELOB KO alters H3K27me3/H3K27M incorporation at thousands of loci and disrupts Pol2 transcriptional activity. |
CRISPR screen and KO, PRO-seq, RNA-seq, ChIP-seq, xenograft models |
bioRxivpreprint |
Medium |
42239282
|