| 2006 |
d-Asb11 knockdown in zebrafish altered expression of neural precursor genes sox2 and sox3, caused expansion of neurogenin1-positive proneural cells followed by premature neuronal differentiation, while forced misexpression of d-asb11 ectopically induced sox2 and abolished neurogenesis. Overexpression in pluripotent and neural-committed progenitor cell lines inhibited terminal neuronal differentiation and enhanced proliferation, establishing d-Asb11 as a regulator of neural progenitor compartment size that maintains precursors in an undifferentiated proliferating state, possibly through control of SoxB1 transcription factors. |
Morpholino knockdown, forced misexpression in zebrafish embryos, overexpression in progenitor cell lines, HuC labeling, sox2/sox3/neurogenin1 expression analysis |
The Journal of cell biology |
High |
16893969
|
| 2008 |
d-Asb11 is an essential mediator of canonical Delta-Notch lateral inhibition signaling in zebrafish. Morpholino knockdown repressed Delta-Notch elements and their transcriptional targets; misexpression activated Notch reporters cell-non-autonomously. d-Asb11 was shown to specifically ubiquitylate and degrade DeltaA both in vitro and in vivo, identifying DeltaA as a direct substrate for ASB11-mediated ubiquitination and degradation. |
Morpholino knockdown, misexpression in zebrafish embryos, Notch reporter assays (cell-autonomous and non-autonomous), in vitro and in vivo ubiquitylation and degradation assays for DeltaA |
Nature cell biology |
High |
18776899
|
| 2010 |
The Cul5 box domain of d-Asb11 is required in vivo for proper Notch signaling and neural cell fate. A zebrafish mutant lacking the Cul5 box (Asb11(Cul)) was defective in Notch signaling, unable to degrade DeltaA during embryogenesis, showed impaired neural cell fate specification, and Asb11(Cul) mRNA failed to transactivate a her4::gfp Notch reporter. This establishes that the Cul5 box domain is essential for d-Asb11 function in the ECS ubiquitin ligase complex. |
Zebrafish Cul5-box domain mutant generation and characterization, Notch target gene expression, DeltaA degradation assay in vivo, her4::gfp reporter assay |
PloS one |
High |
21124961
|
| 2012 |
Asb11 localizes specifically to Pax7+ muscle satellite cells across vertebrates. Forced expression of d-asb11 impaired terminal differentiation and caused enhanced proliferation in myogenic progenitors in vivo and in vitro. A germline hypomorphic zebrafish d-asb11 mutation caused premature differentiation of muscle progenitors and delayed regenerative responses in adult injured muscle, establishing d-Asb11 as a principal regulator of embryonic and adult regenerative myogenesis. |
Expression/localization analysis (Pax7+ satellite cell compartment), forced overexpression in zebrafish and cell lines, germline hypomorphic zebrafish mutant, adult muscle regeneration assay |
Stem cells and development |
High |
22512762
|
| 2013 |
ASB11 is a novel endoplasmic reticulum-resident ubiquitin ligase that interacts with and promotes ubiquitination of Ribophorin 1, an integral component of the oligosaccharyltransferase (OST) glycosylation complex. Expression of ASB11 increases Ribophorin 1 protein turnover in vivo. ASB11 was also found to form complexes with Cullin 5 and Elongins B/C, and Cullin 5 complexes can oligomerize. |
SILAC-based protein/protein interaction analysis, Co-IP, in vivo ubiquitination assay, protein turnover assay, subcellular localization (ER-resident) |
The Journal of biological chemistry |
High |
24337577
|
| 2019 |
Cul5-ASB11 is the E3 ligase that ubiquitinates the pro-apoptotic protein BIK, targeting it for degradation. ER stress activates ASB11 through the IRE1α-XBP1s arm of the unfolded protein response, stimulating BIK ubiquitination, interaction with p97/VCP, and proteolysis, thereby promoting cell survival during ER stress adaptation. Genotoxic agents down-regulate this IRE1α-XBP1s-ASB11 axis to stabilize BIK, contributing to apoptosis. XBP1s was identified as the transcriptional activator of ASB11 in response to ER stress. |
Co-IP, ubiquitination assay, knockdown/overexpression, IRE1α inhibitor treatment, ER stress induction, genotoxic agent treatment, cell survival/apoptosis assays |
The Journal of cell biology |
High |
31387940
|
| 2022 |
The aspariginyl hydroxylase FIH (factor inhibiting HIF) catalyzes hydroxylation of asparaginyl residues in ankyrin repeat domain-containing proteins including ASB11. Biochemical and crystallographic evidence showed that FIH hydroxylates both asparaginyl residues in 'VNVN' motifs of ASB11's ankyrin repeat domain, representing a post-translational modification of ASB11. |
Biochemical hydroxylation assay, X-ray crystallography, mass spectrometry |
The Journal of biological chemistry |
High |
35537551
|
| 2023 |
The Cul5/ASB11-based ubiquitin ligase polyubiquitinates PAICS (a de novo purine synthesis enzyme) with K6-linked chains, driving purinosome assembly via phase separation. Polyubiquitinated PAICS recruits UBAP2, a ubiquitin-binding protein with intrinsically disordered regions, inducing phase separation for purinosome assembly and enhancing de novo purine synthesis flux. In melanoma, ASB11 is upregulated by relief of H3K9me3/HP1α-mediated transcriptional silencing, leading to constitutive purinosome formation required for melanoma cell proliferation and tumorigenesis. |
Ubiquitination assay (K6-linkage identification), Co-IP, phase separation assay, ASB11 knockdown/overexpression, xenograft tumor model, chromatin immunoprecipitation (H3K9me3/HP1α), DNPS flux assay |
Molecular cell |
High |
37848033
|
| 2024 |
UBE2F neddylates CUL5 to activate CRL5-ASB11 E3 ligase, which ubiquitylates DIRAS2 for degradation. Ube2f deletion in a mouse KrasG12D PDAC model inactivates Mapk-c-Myc signaling by blocking DIRAS2 ubiquitylation, suppressing pancreatitis and pancreatic intraepithelial neoplasia. DIRAS2 deletion largely rescues Ube2f-deletion phenotypes, establishing UBE2F-CRL5ASB11-DIRAS2 as an oncogenic axis in pancreatic cancer. |
Genetic mouse KrasG12D PDAC model with Ube2f deletion, DIRAS2 knockout/rescue experiments, ubiquitylation assay, Mapk-c-Myc signaling readouts, epistasis analysis |
Developmental cell |
High |
38574733
|
| 2026 |
Under hypoxia, FIH-dependent hydroxylation of ASB11 at asparagine residues 90 and 92 is impaired, which enhances ASB11-mediated degradation of ERLIN1. ERLIN1 stabilizes the INSIG1-SCAP-SREBP2 axis to maintain cholesterol homeostasis in hepatocellular carcinoma. Pharmacological targeting using zoledronic acid weakens the ASB11-ERLIN1 interaction and restores cholesterol homeostasis, establishing ERLIN1 as a substrate of ASB11 regulated by FIH hydroxylation. |
In vitro and in vivo HCC models, FIH hydroxylation assay at specific Asn residues, Co-IP (ASB11-ERLIN1 interaction), subcutaneous and orthotopic mouse tumor models, zoledronic acid pharmacological intervention |
Clinical and molecular hepatology |
Medium |
41668292
|